Pinacol-pinacolone Rearrangement Research Articles

Cordierite honeycomb supported Mo(VI)/ZrO2 for Microwave assisted Pinacol-Pinacolone rearrangement

ZrO2, Mo(VI)/ZrO2 and Pt-SO42-/ZrO2 supported on honeycomb monoliths were prepared and characterized for their physico-chemical propertiess such as surface acidity, crystallinity, functionality and morphology. These materials were used as solid acid catalysts in the pinacol rearrangement of benzopinaol via microwave irradiation. Few diols were also subjected to pinacol rearrangment to obtain high yield of rearrangement products with good selectivity. Optimization of reaction conditions was also studied to determine most suitalbe for the effective synthesis pinacolone derivatives. Up to 98% conversion of benzopinacol was achieved under a set of optimised reaction conditions. A reactivation and reusbility study of zirconia basd solid acids was also taken up.

Unexpected phenyl group rearrangement of Thiele’s hydrocarbon derivative under polycyclic aromatic hydrocarbon synthesis

An unexpected ketone was obtained in the synthesis of tetrabenzo[a,d,j,m]coronene having tert-butyl groups from Thiele’s hydrocarbon derivative. The structure of the product was confirmed by not only spectroscopic but also diffraction studies. This product was formed by the rearrangement reaction of one phenyl group and this reaction could be analogous to the pinacol-pinacolone rearrangement.

One-Step Production of 1,3-Butadiene from 2,3-Butanediol Dehydration.

We report the direct production of 1,3-butadiene from the dehydration of 2,3-butandiol by using alumina as catalyst. Under optimized kinetic reaction conditions, the production of methyl ethyl ketone and isobutyraldehyde, formed via the pinacol-pinacolone rearrangement, was markedly reduced and almost 80 % selectivity to 1,3-butadiene and 1,3-butadiene could be achieved. The presence of water plays a critical role in the inhibition of oligomerization. The amphoteric nature of γ-Al2 O3 was identified as important and this contributed to the improved catalytic selectivity when compared with other acidic catalysts.

Synthesis and transformations of 5,5-disubstituted 3-alkenyloxolan-2-ones

By alkylation of 4,4-disubstituted 2-(ethoxycarbonyl)butanolides new 4,4-disubstituted 2-alkenyl-2-(ethoxycarbonyl)butanolides were synthesized, which at alkaline hydrolysis formed 4,4-disubstituted 2-alkenylbutanolides. By oxidation of the latter with hydrogen peroxide and formic acid diololactones were obtained that in conditions of pinacol-pinacolone rearrangement and oxidation with lead tetraacetate afforded formyl- and epoxybutanolides of new structure.

BF3-Et2O mediated skeletal rearrangements of norbornyl appended cyclopentanediols.

An unusual cascade rearrangement has been noticed as a competitive reaction during the treatment of norbornyl appended cyclopentanediols with a Lewis acid (LA): a BF3-Et2O mediated pinacol-pinacolone rearrangement. Deketalization and pinacolone rearrangement occur at two different sites in the molecule and are responsible for the observed cascade rearrangement product. However, deketalization appears to be triggering the cascade steps. The kinetically more stable pinacolone product with an exo-Me group was observed in the case of the bromo analogue, whereas, the thermodynamically more stable pinacolone product with an endo-Me group was observed in the case of the chloro analogue. Epimerization via tautomerization of one diastereomer to the other diastereomer under Lewis acid reflux conditions is possible. On the contrary, the diol equivalent epoxides provide only the diastereomeric mixture of pinacolone products under similar LA reaction conditions. The lower yields observed in the case of the epoxides are due to unwanted side reactions taking place between the two competitive reactive centers, namely, ketal and epoxide. Further, a sequence of elimination, nucleophilic substitution and Ritter type hydrolysis reactions of the epoxides resulted in unexpected elimination products. This transformation not only facilitates a regioselective epoxide opening, but also provides a new route for the preparation of allylic amides of the norbornyl appended cyclopentane ring system.

Multiple One-Pot Reaction Steps using Organically Doped Metallic Hybrid Catalyst

The recently developed family of molecularly doped metals(molecule@metal) has opened the possibility of an interesting,useful concept in catalysis: Entrapment of an organic catalystwithin a catalytic metal leads to a hybrid material capable ofmultiple catalytic steps in one pot. In this report we show thefeasibility of this idea by effecting catalytic dehydration, cata-lytic disproportion, and catalytic hydrogenation, all by usingNafion@Pd. Palladium, in this case, serves not only as a metallicheterogenization matrix—by itself a new heterogenizationmethodology (see below)—but it also serves in its classicalrole as a versatile catalyst. Examples of the successful use ofthis methodology for metal heterogenization of homogeneouscatalysts include the acid-catalyzed pinacol–pinacolone rear-rangement with Nafion entrapped in silver (Nafion@Ag); thedehydration of 2-phenylethanol to styrene with the same cata-lyst;

Synthesis and biological evaluation of new paclitaxel analogs and discovery of potent antitumor agents.

Reaction of 10-deacetylbaccatin III (III) and its 7-TES derivative (IV) with DAST under various conditions resulted in the formation of an array of new fluorinated and non-fluorinated 13-keto taxoid compounds (2a–4a) through a vinylogous pinacol–pinacolone rearrangement. Further fluorination of some of these products (2a, 3a) with NFSi or Selectfluor gave additional derivatives. Sodium borohydride reduction of the 13-keto group of these products (2a, 2b, 3a, 3b, 4a, 8, 9, 11–14) led to a series of 9α-hydroxy taxoid derivatives, which were esterified using the docetaxel side chain employing the corresponding protected β-lactam, followed by deprotection to furnish a library of docetaxel analogs and related compounds. A selected number of synthesized compounds (7, 10, 19a, 19b, 21a, 21b, 23, 27, 29, 34–36) were submitted to the National Cancer Institute (NCI) 60 cell line screening program and tested for cytotoxic properties. Taxoids 19a, 19b, 21a, 21b, 23, 27, 29, 34 and 35 were found to exhibit significant anticancer activity against various cancerous cell lines with 23, 27, and 29 being the most potent compounds, demonstrating GI50 values of ≤5 nM in several assays.

Synthesis, Spectroscopic, and in Vitro Photosensitizing Efficacy of Ketobacteriochlorins Derived from Ring-B and Ring-D Reduced Chlorins via Pinacol–Pinacolone Rearrangement

In this report, we present a regioselective oxidation of a series bacteriochlorins, which on reacting with either ferric chloride (FeCl(3)) or 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) yielded the corresponding ring-B or ring-D reduced chlorins. The effect of the number of electron-withdrawing groups present at the peripheral position, with or without a fused isocyclic ring (ring-E), did not make any significant difference in regioselective oxidation of the pyrrole rings. However, depending on the nature of substituents, the intermediate bis-dihydroxy bacteriochlorins on subjecting to pinacol-pinacolone reaction conditions gave various ketochlorins. The introduction of the keto-group at a particular position in the molecule possibly depends on the stability of the intermediate carbocation species. The newly synthesized bacteriochlorins show strong long-wavelength absorption and produced significant in vitro (Colon26 cells) photosensitizing ability. Among the compounds tested, the bacteriochlorins containing a keto-group at position 7 of ring-B with cleaved five-member isocyclic ring showed the best efficacy.

ChemInform Abstract: Synthesis of a Simple Model Compound of Dynemicin and Cycloaromatization with Pinacol-Pinacolone Rearrangement in the Strained Enediyne Medium Ring.

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ChemInform Abstract: Tandem Carbonyl Coupling-Rearrangements Promoted by the Niobium(III) Reagent. Dual Reductive and Lewis Acid Properties of NbCl3(DME).

Abstract Benzaldehyde (1a) and acetophenone (6) are shown to undergo highly stereoselective reductive couplings by NbCl3(DME). When the reaction is performed at −10°C, the threo diols can be isolated. The intermediate niobiopinacols reveal the ability of subsequent transformations, due to the Lewis acid properties of the reagent used. Starting from 1a stereospecific acetalization leads to threo-2,4,5-triphenyl-1,3-dioxolane (3a), whereas 3,3-diphenyl-2-butanone (7) is obtained from 6 in a pinacol-pinacolone type rearrangement. Alkenes may also be formed in the competing, temperature controlled deoxygenation The stereoselectivity and the easy control of NbCl3 (DME) mediated reactions make it a promising reagent for further synthetic applications.

A facile and efficient pinacol–pinacolone rearrangement of vicinal diols using ZnCl2 supported on silica as a recyclable catalyst

An efficient pinacol rearrangement of variety of primary, secondary and tertiary, symmetrical as well as asymmetrical diols has been investigated using ZnCl2/SiO2 (silzic) as solid acid catalyst. The catalyst is prepared by co-grinding silica gel with anhydrous ZnCl2 followed by thermal activation. The nature of interaction has been investigated using powder XRD, TG-DTA and DSC analyses, FT-IR spectroscopy and by testing the catalytic properties in pinacol–pinacolone rearrangement. FT-IR spectra of catalyst using pyridine as probe molecule shows presence of predominant Lewis acid sites. The results of FT-IR, TG-DTA, DSC analyses and XRD indicated that dispersed ZnCl2 co-ordinates with surface hydroxyl groups leading to formation of a new zinc ion species of –O–Zn–Cl as Lewis acid sites. Various highly substituted aldehydes and ketones were obtained in high isolated yield with excellent selectivity. The catalyst was found to be highly efficient and reusable without any loss of activity. The fact that ZnCl2 did not leach in presence of 1,2-dichloroethane as solvent makes silzic an alternative heterogeneous acid catalyst for pinacol rearrangement to the conventional homogeneous acids. The other interesting facet of this communication is highly efficient synthesis of cyclic spiroketones using silzic as reusable solid acid catalyst hitherto unknown.

Synthesis and Some Transformations of 2‐Alkenyl‐4‐alkoxymethylbutanolides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Facile and Efficient Pinacol Rearrangement Using Tungstophosphoric Acid (H3PW12O40) under Solvent-free Conditions

The pinacol-pinacolone rearrangement is a typical 1,2rearrangement reaction of vicinal diols under acidic conditions which has been known since 1960. This rearrangement involving a dehydration and skeletal rearrangement is one of the earliest documented Wagner-Meerwein rearrangements in carbocation chemistry and has been used as a key step in organic synthesis. The intermediate cations are usually generated under Lewis or Bronsted acid conditions which often result in regioisomeric mixtures of ketones and aldehydes when unsymmetrical diols are used. Regioselectivity is determined by stability of the primary formed carbocation as well as migratory aptitude of the diol substituents which in turn are predicted by stereoelectronic factors. Because of the influence of these factors, it has not been possible to determine an unambiguous migatory order for substituents in the pinacol rearrangement. However, some general trends are discernible. Various studies on the relative migratory aptitudes in the pinacol rarrangement have been conducted. In general, the relative migratory tendency of aryl > alkenyl > hydride > alkyl is observed. Organic reactions are found to occur efficiently under solvent-free conditions and many examples have been reported so far. Heteropoly acids are the object of research for a long time. Much work has been done and there are several commercial processes utilizing heteropoly compounds. In this work we report the usage of heteropoly acids such as tungstophosphoric acid (H3PW12O40) as solid acid for pinacol rearrangement. It is a commercially available and cheap crystalline compound. Also, it is easy to handle and in comparison to the results obtained by carrying out the reaction using other acids, the reaction using tungstophosphoric acid (H3PW12O40) proceeds more efficiently under much milder conditions during a shorter reaction time. When a mixture of 1 : 3 molar ratio of diol and H3PW12O40 are ground at room temperature the products of rearrangement are obtained in high yield. Similar results are obtained by tungstosilicic acid but the conversion percents are lower and leads to formation of some byproducts. Heteropoly acids as solid acids in Pinacol rearrangement affects the migratory aptitude of groups as well as conversions and facility of the reaction process. As the results of Table 1 show the aryl anions migrate more easily than hydride does. Diol 1 led to aldehyde 1a, exclusively, which results from para-methoxyphenyl migration and the product of hydride migration was not obtained under the reaction condition. Diol 4 led to rearrangement products, aldehyde 4a and ketone 4b, which are obtained in ratio of 1:2.1 by paramethoxyphenyl and phenyl migrations, respectively. As it can be seen again no hydride migration is observed under the reaction condition. In the case of 4 because of the greater resonance stabilization of the carbonium ion (4c, Scheme 1), caused by methoxy group, gives mainly the thermodynamically controlled product 4b. Therefore, the reaction of 4 is accelerated because of the greater stability of the carbcatonic intermediate. Pinacol 5 is rearranged to aldehyde 5a and ketone 5b in the ratio of 1:0.5 which are obtained by paramethylphenyl and phenyl migrations, respectively. In the case of 5 the carbocation adjacent to the two phenyl groups is more stable and the reaction led to thermodynamically controlled product 5a. Diol 3 led to aldehyde 3a and ketone 3b in the ratio of 1:0.37. Aldehyde 3a is obtained by phenyl migration and ketone 3b may be obtained by phenyl and/or hydride migration. However, we have no evidence to show that if phenyl or hydride migration has occurred to produce ketone 3b but if we compare this reaction with entries 4 and 5, we may anticipate that the ketone is obtained by phenyl migration and the reaction is thermodynamically controlled. The same trend was observed for rearrangement of 6 which led to 6a in 95% yield. Anthrapinacol 8 gave bianthryl as a dehydration product under the reaction condition. In summary we have shown that pinacol rearrangement is easily carried out by tungstophosphoric acid (H3PW12O40) under solvent-free conditions. Aryl groups migrate more easily than hydride does and the reaction is thermodynamically controlled.

Synthesis and some transformations of 2-alkenyl-4-alkoxymethylbutanolides

The alkylation of 4-alkoxymethyl-2-ethoxycarbonylbutanolides led to the formation of 2-alkenyl-4-alkoxymethyl-2-ethoxycarbonylbutanolides which at alkaline hydrolysis provided new 2-alkenyl-4-alkoxymethylbutanolides. By oxidation of the latter with a mixture of hydrogen peroxide and formic acid 4-alkoxymethyl-2-(2-R-2,3-dihydroxy)propylbutanolides were obtained. The diololactones were shown to suffer under the conditions of the pinacol-pinacolone rearrangement a conversion into previously unknown formyl-and epoxylactones.

Transannular Hydride Migration in Pseudo‐Geminally Substituted [2.2]Paracyclophanes: A Vinylogous Pinacol Rearrangement

AbstractA vinylogous pinacol–pinacolone rearrangement is reported that takes place although the two hydroxyl groups are formally separated by seven bonds. It involves a transannular hydride shift that occurs between the benzylic positions of the pseudo‐geminally substituted [2.2]paracyclophanes 1a–c, 7, 8 and 9. Under mild acidic conditions the corresponding pseudo‐geminally substituted cyclic ethers were established as stable intermediates. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Silver Doped with Acidic/Basic Polymers: Novel, Reactive Metallic Composites

We report the preparation and properties of metallopolymeric composites with acidic and basic properties. The composites are prepared via the recently developed method of entrapping organic molecules within metals. Specifically, we describe the entrapment of the polyacid Nafion or the polybase poly(vinylbenzyltrimethylammonium hydroxide) within silver. The resulting acidic or basic metallic composites decrease or increase, respectively, the pH of water through an ion-exchange process. Furthermore, silver doped with Nafion can be employed as an acid catalyst, as shown for the pinacol–pinacolone rearrangement and for the dehydration of an alcohol. Characterization of these novel materials via microscopy and adsorption studies reveals a three-level hierarchical structure: clusters of ≈ 10 μm in size built from ≈ 1 μm aggregates of ≈ 100 Å silver crystals. Thermogravimetric analysis of the entrapped polymers reveals a catalytic effect of the metal on this process. The two polymers are entrapped differently, and the differences are discussed. Applications ranging from ion-exchange electrodes to bifunctional catalysts are envisaged.

Pinacol‐Pinacolone Rearrangement on FeCl3 Modified Montmorillonite K10.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Molecular orbital studies on the Wagner-Meerwein migration in some acyclic pinacol—pinacolone rearrangements

The semi-empirical PM3 SCF-MO method is used to investigate the Wagner-Meerwein migration of various groups during the pinacol-pinacolone rearrangement of some acyclic systems. Pinacol first protonates and dehydrates to form a carbocation that undergoes a 1,2-migration to form a protonated ketone, which then deprotonates to yield the pinacolone product. We study the Wagner-Meerwein migration of hydride, methyl, ethyl, isopropyl,t- butyl, phenyl and heterocylic 2-, 3-and 4-pyridyl groups in various acyclic 1,2-diol (pinacol) systems as they rearrange to pinacolones. This 1,2-migration involves a three-centred moiety in the cationic transition state. The migratory aptitude predicted here follows the order: hydride >t-butyl > isopropyl > ethyl > methyl > phenyl, which accords well with available experimental data and/or chemical intuition, reflecting also on the ability of the group involved to carry positive charge in the transition state. The structure of the migrating group (whether aliphatic or aromatic) within the transition state also supports the stabilising role of delocalisation of positive charge for reaction feasibility. Geometrical and thermodynamic considerations coincide in assigning the following order to relative “earliness” of the transition state along the reaction pathway:t-butyl > isopropyl > phenyl > methyl > 2-pyridyl > 4-pyridyl

Pinacol-Pinacolone Rearrangement on FeCl3 Modified Montmorillonite K10

Pinacol-pinacolone rearrangement was investigated over Fe-modified montmorillonite K10 catalysts in liquid phase. Exceptional activity was found to be associated with FeCl3 impregnated on K10 through its acetonitrile solution. 100% conversion of benzopinacol was observed in 10 minutes. The catalysts are recyclable.

Effect of various acids at different concentrations on the pinacol rearrangement

The formation of side products in the pinacol–pinacolone rearrangement was studied as a function of concentration and strength of various aqueous acids using 1H NMR spectroscopy. In all cases, pinacolone was the principal product and in most cases, its relative yield decreased with respect to 2,3-dimethyl-1,3-butadiene, when the acid concentration was lowered or the corresponding conjugate base was added.