Mannich Condensation of 3,3,5-Trimethylcyclohexanone and Its Oxime

Mannich condensation of 3,3,5-trimethylcyclohexanone with paraformaldehyde and dimethylamine or benzylamine hydrochloride involves both activated methylene group in the initial ketone to give compounds with equatorial aminomethyl substituent. The major isomer is that formed by addition at the less sterically hindered carbon atom. Likewise, Mannich condensation of the E and Z isomers of 3,3,5-trimethylcyclohexanone oxime react at both methylene groups, and the addition of aminomethyl fragment occurs preferentially at that methylene group which is located more closely to the oxime hydroxy group.     

Heterogeneously catalyzed asymmetric C=C hydrogenation: origin of enantioselectivity in the proline-directed Pd/isophorone system

We have studied the proline-directed, Pd-catalyzed enantioselective hydrogenation of isophorone in the liquid state using a variety of methods. Our results unambiguously reveal the true reaction pathway and demonstrate that all earlier mechanistic hypotheses are wrong: although a proline/isophorone condensation product is formed, it is merely a spectator and not a key reaction intermediate in subsequent heterogeneous hydrogenation. Enantioselectivity is the result of kinetic resolution-a process that occurs homogeneously in solution and not at the metal surface. Racemic 3,3,5-trimethylcyclohexanone (TMCH) is produced by initial heterogeneous hydrogenation of isophorone; proline then reacts homogeneously, preferentially with one enantiomer of TMCH, leaving an excess of the other. Thus in complete contrast to the case of ketoester asymmetric hydrogenation, the metal surface is not involved in the crucial enantio-differentiation step. The mechanism we propose also explains why the maximum attainable yield of enantiopure TMCH cannot exceed 50%.     

Mechanistic insights into the proline-directed enantioselective heterogeneous hydrogenation of isophorone

The adsorption rates onto a range of platinum single-crystal surfaces of key species involved in the proline-directed heterogeneous enantioselective hydrogenation of isophorone were investigated by electrochemical means. Specifically, the uptakes of the prochiral reactant (isophorone), the chiral hydrogenation product (3,3,5-trimethylcyclohexanone), and the chiral directing agent ((R)- and (S)-proline) were examined. The effects of R,S chiral kink sites on the adsorption of (R,S)-proline were also studied. The reactant adsorbs approximately 105 times faster than the chiral modifier so that under conditions of competitive adsorption the latter is entirely excluded from the metal surface. Supplementary displacement and reaction rate measurements carried out with practical Pd/carbon catalysts show that under certain reaction conditions isophorone quickly displaces preadsorbed proline from the metal surface. Thus both kinetics and thermodynamics ensure that the chiral modifier can play no role in any surface-mediated process that leads to enantiodifferentiation. These results are fully consistent with the recent proposal1 that the crucial step leading to enantiodifferentiation occurs in the solution phase and not at the metal surface. In addition, it is found that there is no preferred diastereomeric interaction between (R,S)-proline and R,S step kink sites on Pt{643} and Pt{976}, implying that such sites do not play a role in determining the catalytic behavior of supported metal nanoparticles.     

Synthesis and properties of carbamoyl derivatives of 5-hydroxy-3,3,5-trimethylisoxazolidine

The reaction of 5-hydroxy-3,3,5-trimethylisoxazolidine with alkyl (or aryl) isocyanates gives N-alkyl(aryl)-carbamoyl-5-hydroxy-3,3,5-trimethylisoxazolidines, which react with methanol in the presence of p-toluenesulfonic acid to give 5-methoxy-1-carbamoyl derivatives of isoxazolidine. When arylcarbamoyl-5-hydroxy-3,3,5-trimethylisoxazolidines are heated in carbon tetrachloride, they are converted to O-arylcarbamoyl-N-(2-methyl-4-oxo-2-pentyl)hydroxylamines, the treatment of which with hydrogen chloride in benzene made it possible to isolate 1,2,6-oxadiazepin-7-ones along with the hydrochloride of the given compounds.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 746–750, June, 1979.     

Determination of free and conjugated cis-3,3,5-trimethylcyclohexanol in plasma and urine

A gas chromatographic procedure was developed to determine free and conjugated cis-3,3,5-trimethylcylcohexanol in plasma and urine. The sample is extracted with dichloromethane when free cis-3,3,5-trimethylcyclohexanol is determined, or with hexane after enzymatic hydrolysis, when conjugated cis-3,3,5-trimethylcyclohexanol is determined. An aliquot of the organic extract is injected into a stainless-steel column (packed with Carbowax 20M, 15% on Chromosorb W AW 100-120 mesh) and detected with a flame ionization detector. Extraction recovery from plasma and urine was almost 100% and the limit of quantification was fixed at 100 ng/ml plasma or urine. The procedure was evaluated in a pharmacokinetic study of cyclandelate and its metabolite cis-3,3,5-trimethylcyclohexanol.     

Reaction of 5-hydroxy-3,3,5-trimethylisoxazolidine with acrylic acid esters

The reaction of 5-hydroxy-3,3,5-trimethylisoxazolidine with methyl, ethyl, and tert-butyl acrylates, proceeds as Michael addition, and produces previously, unknown 5-hydroxy-3,3,5-trimethylisoxazolidine-2-propionic acid esters. The structures of the obtained products are proved by¹H and¹³C NMR spectroscopy and by their subsequent transformation into 5-hydroxy-3,3,5-trimethylisoxazolidine-2-propionic acid.Institute of High-Molecular Compounds, Russian Academy of Sciences, St. Petersburg 199004, Russia; St. Petersburg State University, St. Petersburg 198904, Russia Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 945–947, July, 1999.     

Synthesis of 2-Methacryloyl-5-hydroxy-3,3,5-trimethylisoxazolidine and Copolymers Thereof

Previously unknown 2-methacryloyl-5-hydroxy-3,3,5-trimethylisoxazolidine was prepared by the reaction of 5-hydroxy-3,3,5-trimethylisoxazolidine with methacryloyl chloride. Homopolymers of this compound and its copolymers with N-vinylformamide and N-vinylpyrrolidone were obtained by radical polymerization.     

Reaction of 4,5-Dihydro-1H-pyrazole-3,5,5-tricarboxylic Acids Esters with Halogens

Esters of 4-R-4,5-dihydro-1H-pyrazole-3,5,5-tricarboxylic acids with chlorine yield esters of 4-R-5-chloro-4,5-dihydro-3H-pyrazole-3,3,5-tricarboxylic acids that at thermolysis provide the esters of the corresponding 2-chlorocyclopropanetricarboxylic acid. The same esters react with bromine in dichloromethane at room temperature to give a mixture of esters of the corresponding 1H-pyrazole-3,5-dicarboxylic acids and 5-bromo-4,5-dihydro-3,3,5-tricarboxylic acids. From 5,5-diethyl 3-methyl 4,5-dihydro-1Hpyrazole-3,5,5-tricarboxylate and N-iodosuccinimide or a system iodine-silver trifluoroacetate we obtained 1,1-diethyl 2-methyl 2-iodocyclopropane-1,1,2-tricarboxylate.     

Two New Monoterpenes from Mentha haplocalyx Briq.

Two new monoterpenes with a skeleton similar to the 1,8‐cineole skeleton, i.e., (1R,4R)‐3,3,5‐trimethyl‐2‐oxabicyclo[2.2.2]oct‐5‐en‐4‐ol ( 1 ) and (1R,4R)‐4‐methoxy‐3,3,5‐trimethyl‐2‐oxabicyclo[2.2.2]oct‐5‐ene ( 2 ), were isolated from an aqueous acetone extract of the aerial parts of Mentha haplocalyx, together with three known compounds. Their structures were elucidated by extensive spectroscopic methods and by comparison with reference values.     

Diverse chemical behaviour of 2-hydroxy-functionalized pyrroline-1-oxide

The reactivity of 2-hydroxy-3,3,5-trimethyl-3,4-dihydro-2H-pyrrole 1-oxide was investigated. The title compound showed unexpected reactivity with several different types of reagents.     

A New,Specific Synthesis of β-Cyclocitral

A new specific synthesis of ρ-cyclocitral is presented. The key step is the dehydration of the trans 2.2.6-trimethylcyclohexanone cyanohydrin by thionyl chloride.     

Steric vs. electrostatic effects in the nucleophilic addition to a hindered cyclohexanone

The relative importance of steric vs. electrostatic effects in the nucleophilic addition to (4R,6S)-4-(tert-butyldimethylsiloxy)-2,2,6-trimethylcyclohexanone (1), a well-known chiral building block, is investigated.     

Reaction of Chloral With Allyl Alcohols. Synthesis of Substituted 3,3,5-Trichloro-2-hydroxytetrahydropyrans

When heated with substituted allyl alcohols in acetonitrile in the presence of copper monochloride, chloral forms substituted 3,3,5-trichlorotetrahydropyrans as mixtures of diastereomers.     

Total synthesis of (+/-)-cameroonanol

[reaction: see text]The structure and relative stereochemistry of the novel silphiperfolane-type sesquiterpene cameroonan-7alpha-ol (1) were confirmed by a total synthesis of (+/-)-1 from 3,3,5-trimethylbicyclo[3.3.0]oct-1(8)-en-2-one (6) by means of a Sakurai reaction with (Z)-crotylsilane, free radical hydrobromination, base-induced cyclization, and LiAlH4 reduction.     

Über den isomerisierungsmechanismus phenylsubstituierter cyclopropene

The thermal and thermocatalytic isomerisations of methyl 2,3,3-triphenylcyclopropene-1-carboxylate to methyl 2,3-diphenylindene-1-carboxylate have been studied. The rate constants of cyclopropene ring opening were determined and parameters of activation were calculated for the thermal process. The formation of cyclopropene and indene derivatives under the photochemical decomposition of methyl 3,3,5-triphenylpyrazolenine-4-carboxylate is discussed.     

The first synthesis and absolute configuration of glaucescenolide

The first synthesis of glaucescenolide (1), a cytotoxic sesquiterpene isolated from the liverwort, Schistochila glaucescens, was achieved by starting from 2,2,6-trimethylcyclohexanone (2). The absolute configuration of the naturally occurring 1 was confirmed as 5S,7S,10R.     

Some Chemical Conversions of 3,3,5-Trichloro-2-hydroxytetrahydropyran

A series of chemical conversions of 3,3,5-trichloro-2-hydroxytetrahydropyran has been carried proceeding both with ring opening and with its retention. Alkylation, acylation, and sulfonylation of the hydroxyl group of the initial ring have been carried out.     

Incompatible effects of specific acids on the thermokinetics of 1,1-bis(tert-butylperoxy)-3,3,5-trimethylcyclohexane

Journal of Thermal Analysis and Calorimetry - 1,1-Bis(tert-butylperoxy)-3,3,5-trimethylcyclohexane (TMCH), an industrial initiator and cross-linking agent comprising two active peroxy bonds,...     

Structure de modèles de polyesters—3[1] transférabilité de structure état solide (RX,RMN 13C solide) état dissous (RMN 13C, 1H) du bistriméthyl-3,3,5 cyclohexyl phtalate

The structure of bis-3,3,5-trimethyl cyclohexyl phthlate is described for the solid state (X-rays, ¹³C NMR) and in solution (¹³C and ¹H NMR). The results show similarity of structure in the two states.     

Synthese von optisch aktiven,natürlichen Carotinoiden und strukturell verwandten Naturprodukten. I. Synthese der chiralen Schlüsselverbindung (4R, 6R)-4-Hydroxy-2,2,6-trimethylcyclohexanon

Synthesis of optically active natural carotenoids and structurally related compounds. I. Synthesis of the chiral key compound (4R, 6R)-4-hydroxy-2,2,6-trimethylcyclohexanone. A technical synthesis of (4R, 6R)-4-hydroxy-2,2,6-trimethylcyclohexanone ( 7 ) starting from the readily available oxo-isophorone ( 2 ) is described. 7 is an ideal precursor for the synthesis of naturally occurring, optically active hydroxylated carotenoids (e.g. zeaxanthin, cryptoxanthin and structurally related compounds). Chirality is introduced at C(6) by a stereoselective fermentative hydrogenation of the double bond using baker's yeast as the biocatalyst. Thereafter the carbonyl group at C(4) is reduced selectively and stereospecifically by chemical methods to the corresponding alcohol. Chemical reduction is preferably carried out by hydrogenation in the presence of a nickel catalyst or using triisobutylaluminium as the reducing agent. Stability, stereochemistry and physical properties of 7 and the stereoisomers thereof are discussed.