Pummerer's Ketone Research Articles

ChemInform Abstract: Novel Anodic Concepts for the Selective Phenol Coupling Reaction

AbstractReview: 66 refs.

ChemInform Abstract: Cycloaddition of Acylnitroso Compounds and Nitrosobenzene with the Pyrrolidine Dienamine of Pummerer′s Ketone: X-Ray Crystal Structure of a Bridged 1,2-Oxazine Derivative.

When the pyrrolidine dienamine 2 of Pummerer's ketone 1 was treated with nitrosocarbonylmethane 4, generated in situ by periodate oxidation of acetohydroxamic acid, the major product was a bridged 1,2-oxazine, shown to have the structure 10 by X-ray crystallographic analysis. This structure incorporates 2 mol equiv. of nitrosocarbonylmethane with, remarkably, reductive loss of 1 nitroso oxygen, despite the oxidising reaction conditions. The same product was accompanied by a pyrrolidino enone 13 and an acetamido enone 8 when the nitroso dienophile was liberated in situ by retro-Diels–Alder cleavage of the corresponding 9,0-dimethylanthracene cycloadduct 15. The dienamine 2 reacted with nitrosobenzene under various conditions to afford a bridged oxazine 17 incorporating 1 mol equiv. of nitrosobenzene, a phenylamino enone 19, and a bridged amino ketone 20 incorporating 2 equiv. of nitrosobenzene. The last two compounds had also undergone, formally, reductive loss of nitroso oxygen. However, the major product was a nitrogen-free, caged dimer 18 of the 4-oxo derivative of Pummerer's ketone.

ChemInform Abstract: New Synthetic Route to Pummerer′s Ketone.

Abstract Pummerer's ketone 1 is obtained with an overall yield of 55 % by the following sequence: Claisen rearrangement of an arylcyclohexylether 3; allylic oxidation of the methylcycloalkylphenolic derivative 4b, then spontaneous cyclisation during demethylation to give 2. 1 is obtained by dehydrogenation of 2. NMR data agree with a cis stereochemistry at C4a and C 9b.

Laccase-mediated oxidation of phenolic derivatives

The laccase-catalyzed oxidation of para-alkyl phenols (p-cresol, 3,4-dimethylphenol, tyrosol, 2′-O-acetyl-tyrosol) in biphasic systems has been investigated. With all the substrates compounds similar to the so-called “Pummerer's ketone” could be isolated in reasonable yields. Accumulation of this kind of products is due to the fact that these compounds, in contrast to other dimers, are “dead-end” products, as they cannot be further oxidized by the enzyme.

Peroxidase-catalyzed synthesis of neolignan and its anti-inflammatory activity

Different peroxidases were used to catalyze the synthesis of neolignan. Horseradish peroxidase (type I, Sigma) was employed successfully to catalyze the formation of magnolol by the phenolic oxidative coupling of allyphenol. The effects of organic co-solvents, pH, addition rate of H 2O 2, and the ratio of enzyme/substrate on the yields of dimer were studied. After the peroxidase-catalyzed reaction was performed, different neolignans were isolated and identified as magnolol ( 3), the trimeric ortho– ortho-coupled product dunnianol ( 4), the ortho- O-coupled product isomagnolol ( 5), and the Pummerer's ketone derivative ( 6). The inhibitory activities of magnolol against cyclo-oxygenase and lipoxygenase were also reported.

Catalytic Oxidation of p-Cresol by Ascorbate Peroxidase

Transient and steady state kinetics, together with a range of chromatographic and spectroscopic techniques, have been used to establish the mechanism and the products of the H2O2-dependent oxidation of p-cresol by ascorbate peroxidase (APX). HPLC, GC-MS, and NMR analyses are consistent with the formation of 2,2′-dihydroxy-5,5′-dimethylbiphenyl (II) and 4α,9β-dihydro-8,9β-dimethyl-3(4H)-dibenzofuranone (Pummerer's ketone, III) as the major products of the reaction. In the presence of cumene hydroperoxide, two additional products were observed which, from GC and MS analyses, were shown to be 1,1-dimethylbenzylalcohol (IV) and bis-(1-methyl-1-phenyl-ethyl)-peroxide (V). The product ratio II:III was dependent on enzyme concentration: at low concentrations Pummerer's ketone (III) predominates and at high concentrations formation of the biphenyl compound (II) is favored. Steady-state data showed a sigmoidal dependence on [p-cresol] that was consistent with the presence of 2.01 ± 0.15 binding sites for the substrate (25.0°C, sodium phosphate, pH 7.0, μ = 2.2 mM) and independent of ionic strength in the range 2.2–500 mM. Single turnover kinetic experiments (pH 7.0, 5.0°C, μ = 0.10 M) yielded second-order rate constants for Compound I reduction by p-cresol, k2, of 5.42 ± 0.10 × 105 M−1 s−1, respectively. Rate-limiting reduction of Compound II by p-cresol, k3, showed saturation kinetics, giving values for Kd = 1.54 ± 0.12 × 10−3 M and k3 = 18.5 ± 0.7 s−1. The results are discussed in the more general context of APX-catalyzed aromatic oxidations.

Diastereo-differentiating coupling of phenoxy radical moiety controlled by 2,4-pentanediol tether. Preparation of optically active Pummerer's ketone analogs

The highly diastereo-differentiating coupling of the phenoxy radical could be achieved by a 2,4-pentanediol tethered reaction to give a single diastereomer of Pummerer's ketone analog. By the removal of the chiral auxiliary, the optically active phenoxy radical dimer was obtained in good yield.

A Relative of Pummerer's ketone as a Source of Morphine Analogues

An analogue (dibenzofurane derivative) (3) of Pummerer's ketone has been prepared in low yield by intermolecular oxidative coupling of methyl 4-hydroxyphenylacetate. Its key structural feature is the presence in the 9b-position of a CH 2 CO 2 Me group. Conjugate addition of hydrogen cyanide to the αβ-unsaturated ketone system inserts in the 1-position a cyano group trans to the 9b-substituent. Suitable protection of the 3-oxo group, followed by reduction of the 1-cyano group affords a lactam (9), which may be regarded as an analogue of morphine, in which ring B has been ruptured

Studies on the preparation of bioactive lignans by oxidative coupling reaction. III. Synthesis of polyphenolic benzofuran and coumestan derivatives by oxidative coupling reaction of methyl (E)-3-(4-hydroxy-2-methoxyphenyl)propenoate and their inhibitory effect on lipid peroxidation.

Three dihydrobenzofuran derivatives 11, 19, 22, a Pummerer's ketone 20 and a dimeric phenylpropanoid 24 were synthesized by oxidative coupling reaction of methyl (E)-3-(4-hydroxy-2-methoxyphenyl)propenoate 10, which was prepared from umbelliferone. The major product 11 was converted into its acetate 21 and schizotenuin D analogs 27, 28, 29. A new coumestan derivative 13 was synthesized from 29. Ten synthetic compounds thus obtained were tested for inhibitory effects on lipid peroxidation in rat brain homogenate.

New Synthetic Route to Pummerer's Ketone

Abstract Pummerer's ketone 1 is obtained with an overall yield of 55 % by the following sequence: Claisen rearrangement of an arylcyclohexylether 3; allylic oxidation of the methylcycloalkylphenolic derivative 4b, then spontaneous cyclisation during demethylation to give 2. 1 is obtained by dehydrogenation of 2. NMR data agree with a cis stereochemistry at C4a and C 9b.

Cycloaddition of acylnitroso compounds and nitrosobenzene with the pyrrolidine dienamine of Pummerer's ketone: X-ray crystal structure of a bridged 1,2-oxazine derivative

When the pyrrolidine dienamine 2 of Pummerer's ketone 1 was treated with nitrosocarbonylmethane 4, generated in situ by periodate oxidation of acetohydroxamic acid, the major product was a bridged 1,2-oxazine, shown to have the structure 10 by X-ray crystallographic analysis. This structure incorporates 2 mol equiv. of nitrosocarbonylmethane with, remarkably, reductive loss of 1 nitroso oxygen, despite the oxidising reaction conditions. The same product was accompanied by a pyrrolidino enone 13 and an acetamido enone 8 when the nitroso dienophile was liberated in situ by retro-Diels–Alder cleavage of the corresponding 9,0-dimethylanthracene cycloadduct 15. The dienamine 2 reacted with nitrosobenzene under various conditions to afford a bridged oxazine 17 incorporating 1 mol equiv. of nitrosobenzene, a phenylamino enone 19, and a bridged amino ketone 20 incorporating 2 equiv. of nitrosobenzene. The last two compounds had also undergone, formally, reductive loss of nitroso oxygen. However, the major product was a nitrogen-free, caged dimer 18 of the 4-oxo derivative of Pummerer's ketone.

Influence of the reaction medium on the product distribution of peroxidase-catalysed oxidation of p-cresol.

p-Cresol was oxidized by hydrogen peroxide in a reaction catalysed by horseradish peroxidase and the low molecular weight products were investigated. In aqueous media Pummerer's ketone (I) was the dominating product but in organic media the product distribution was quite different; 2,2'-dihydroxy-5,5'-dimethyldiphenyl (II) was the main low molecular weight product. Similar product distributions were obtained with peroxidase adsorbed on a solid support and suspended in toluene and with peroxidase solubilized in a microemulsion containing the same solvent. The best selectivity for the formation of (II) was obtained when the enzyme was adsorbed on Celite and suspended in water-saturated chloroform with 0.5% (v/v) extra water added. The yield of low molecular weight products in this case was 28%; of this fraction, 95% was (II).

Stereochemistry and mechanism of [4 + 2] photocycloaddition of Pummerer's ketone to furan

Reaction du furanne avec la dimethyl tetrahydro dibenzofurannone-3 (cetone de Pummerer). Structure aux RX des cycloadduits (derives d'epoxy-1,4 benzo [b] naphto [1,2-d] furanne)

Stereochemistry and mechanism of the [2 + 2] and [4 + 2] photocycloaddition of alkenes and dienes to pummerer's ketone

Irradiation of Pummerer's ketone (PK) in furan gave the trans-fused [4 + 2] cycloadducts 2 and 3, whose structures were determined by their 1H NMR spectra and confirmed by X-ray crystallography. Irradiation of PK in the presence of tetramethylethylene (TME) gave cycloadduct 4 and with 1,1-dimethoxyethylene (DME) gave [2 + 2] cycloadducts 5,6 and 7, respectively. The X-ray crystal structures of 4—7 show that the four- and six-membered rings of 4 and 7 are trans-fused, and 5 and 6 are cis-fused, respectively. Differential quenching of the formation of cycloadducts 2–5 and 7 by the free radical TEMPO was observed. Formation of cycloadducts 2–4 was also quenched differentially by O 2. A short lived (15 nsec) transient observed on nanosecond flash photolysis of PK is suggested to be a highly twisted triplet excited state, which is the likely precursor of both [4 + 2] and [2 + 2] adducts. It is proposed that stepwise addition of furan and alkenes to PK triplets gives triplet biradicals, which can be intercepted by TEMPO and O 2 , and that these reactions probably do not involve a ground state trans-cyclohexenone intermediate.

Methylene-indolines, indolenines et indoleniniums XVI nouvelle synthese d'hexahydrodibenzofurannes

Nitrous acid deaminated indolenines 1a , b to hemiketals 2a , b , which were reduced (Et 3SiH/TFA) to hexahydrodibenzofurans 7a , b . 7b was identified with a compound prepared from Pummerer's ketone 8 .

Formation of Pummerer's ketone from 4-methylphenoxenium ion. An acid-catalyzed solvolysis of N-p-toluenesulfonyl-O-(4-tolyl)-hydroxylamine in p-cresol.

La reaction du titre en presence d'acide trifluoroacetique conduit au p-toluenesulfonimidate d'hydroxy-6 m-tolyle et, par l'intermediaire de la reaction entre le p-cresol et un ion p-tolyl oxenium au dimethyl-5,5' biphenylediol-2,2' et a la cetone de Pummerer

Some chemical transformations of pummerer's ketone

The relative proportions of the epimeric alcohols obtained by reducing Pummerer's Ketone with a range of reagents have been determined, and the stereochemistries of these alcohols confirmed by europium shift studies. The reactions of Pummerer's Ketone with phenylcuprate, N,N-diethylaminopropyne, tosmic and hydrazoic acid have been investigated.

Some basic derivatives of pummerer's ketone.

AbstractThe use of Pummerer's ketone as pharmacophoric synthon is described and a preliminary account of the pharmacological properties of the new derivatives, basic esters, is given.

Stereochemistry of the photoinduced addition of methanol to Pummerer's ketone, a 2-cyclohexenone

Stereochemistry of the photoinduced addition of methanol to Pummerer's ketone, a 2-cyclohexenone

On the oxidation of 2-t-Butyl-p-cresol

While oxidation of alkaline solutions of 2-t-butyl-p-cresol by ferricyanide or silver oxide gives the ortho-para-coupled Pummerer's ketone (6), ferric chloride in slightly acid solution gives the ortho- coupled biphenyldiol (5). With ddq in methanol the cresol is further oxidized, again through ortho coupling, to the lactone (10), in which one of the aromatic rings has been cleaved, and to the dibenzo-furan (9). Minor products, both monomeric and dimeric, in which the methyl group has been oxidized via the quinone methide, were also identified.