Parent Ketone Research Articles

CARO'S ACID SUPPORTED ON SILICA GEL, PART VIII: AN EFFICIENT AND SELECTIVE REAGENT FOR CONVERSION OF PHENYLHYDRAZONES AND SEMICARBAZONES TO THE CORRESPONDING CARBONYL COMPOUNDS

Deprotection of phenylhydrazones and semicarbazones to their parent aldehydes and ketones in high yields has been carried out using caro's acid supported on silica gel as a selective oxidant under mild conditions.

1,4-hydroxybiradical behavior revealed through crystal structure-solid-state reactivity correlations.

Structure-reactivity correlations for triplet 1,4-hydroxybiradicals in solution are made difficult by the presence of multiple reactive conformers and the possibility of conformation-dependent intersystem crossing. These problems can be overcome by working in the crystalline state, where the conformations of the 1,4-hydroxybiradicals are fixed and determinable by X-ray crystallography of the parent ketones, assuming that hydrogen atom abstraction occurs with little or no change in conformation. This approach is applied to 15 bi- and tricyclic ketones designed to have slightly different biradical conformations, so that the effect of small and incremental changes in geometry on biradical behavior can be tested. The results indicate that, while geometry does have a strong influence on 1,4-hydroxybiradical partitioning between cyclization, cleavage, and reverse hydrogen transfer, a full understanding of the results requires that the strain involved in forming the cyclization products be taken into account.

Photochemical and Beckmann rearrangement of (Z)-cholest-4-en-6-one oxime

Beckmann rearrangement of (Z)-cholest-4-en-6-one oxime (4) (prepared in 4 steps starting from cholest-5-en-3?-ol ?1)) with thionyl chloride in dioxane solution afforded an enamide-type lactam, i.e. 7-aza-B-homocholest-4-en-6-one (6) as a single product. Photoreaction of the same compound in methanol or benzene-acetic acid solution gave a mixture of products, with the formation of the parent ketone 3 and the occurrence of Z/E isomerization, while the lactam 6 was obtained only when the reaction was performed in methanol and then in very low yield (7%).

Benzyltriphenylphosphonium Peroxodisulfate (PhCH2PPh3)2S2O8: An Efficient and Convenient Reagent for the Oxidative Cleavage of Phenylhydrazones, Paranitrophenylhydrazones, and Semicarbazones to Their Parent Carbonyl Compounds

Deprotection of phenylhydrazones, paranitrophenylhydrazones, and semicarbazones to their parent aldehydes and ketones in high yields has been carried out using benzyltriphenylphosphonium peroxodisulfate as a selective oxidant under mild conditions.

11β-Hydroxysteroid dehydrogenase type 1: tissue-specific expression and reductive metabolism of some anti-insect agent azole analogues of metyrapone

The azole analogues of metyrapone are novel candidates for selective anti-insect agents that inhibit the synthesis of 20-hydroxyecdysone (20E), the moulting hormone of insects. Metyrapone, which is a model substrate for studying the reductive properties of oxidoreductases, is itself effectively reduced to the corresponding alcohol by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD 1). For this reason, the ability of 11β-HSD 1 to metabolize the metyrapone analogues as well was studied. In addition, the expression (by Western blots) and activity (reduction/oxidation of dehydrocorticosterone/corticosterone) of 11β-HSD 1 in different male and female mouse tissues were investigated. Xenobiotic carbonyl reductase activities in these tissues were assessed with metyrapone as a model substrate. The kinetic parameters of 11β-HSD 1 with metyrapone analogues as substrates were calculated after high-pressure liquid chromatography (HPLC) determination of the product alcohols. Our results indicate that the novel insecticides are extensively metabolized by mouse 11β-HSD 1. Moreover, the resulting alcohols are not only less toxic than the parent ketones but also have the potential, owing to the newly formed hydroxyl group, to be eliminated from the body by consecutive phase II reactions. Thus, the new metyrapone analogues may be potential anti-insect agents, safer for humans due to their reductive detoxification, mainly by the hepatic 11β-HSD 1, and selectively affecting insect development by inhibiting ecdysone 20-monooxygenase (E-20-M).

Triplet Excited States and Radical Intermediates Formed in Electron Pulse Radiolysis of Amino and Dimethylamino Derivatives of Benzophenone

The electron pulse radiolysis technique has been used to study the spectral, kinetic, and radiation chemical properties of the triplet excited states as well as the reduced and oxidized radicals of 2-amino, 4-amino-, 4-(dimethylamino)-, and 4,4‘-bis(dimethylamino)benzophenones. Hydrated electron ( ) has been found to react with these benzophenone derivatives to form the anion radical species with the rate constants varying from (4 to 10) × 109 dm3 mol-1 s-1, which are slower than that for the parent ketone, benzophenone. The spectral and kinetic properties of the transient ketyl and anion radicals have been studied by generating them at suitable pH. The absorption peaks of the ketyl radicals appear in the region 565−630 nm and those of the anion radicals are red shifted in the wavelength region 565−630 nm. The pKa values of the ketyl ⇔ anion radical equilibria vary from 8.8 to 10.7 for various substituted aminobenzophenones. The cation radicals of these derivatives have been generated by pulse radiolysis in 1,2-dichloroethane and tetrachloromethane solvents along with other transient species, such as ion pairs and radical adducts. The triplet states of these compounds have been generated in benzene. The probable mechanism of the self-quenching interaction between the triplet and the ground state is the simple hydrogen atom abstraction reaction by the nπ* triplet, which is energetically close to the lower lying ππ* triplet state. Mechanisms of interaction between the ground states of the amino-substituted benzophenone derivatives and the benzophenone triplet have been found to depend on the driving force for the charge- or electron-transfer reaction between the members of a particular pair. nπ* Triplet state of benzophenone interacts with 2-aminobenzophenone via energy transfer to the latter, with 4-aminobenzophenone via hydrogen atom abstraction and with 4-(dimethylamino)- and 4,4‘-bis(dimethylamino)benzophenones by electron-transfer coupled with proton-transfer reactions. Only in the case of the interaction between triplet benzophenone and 4-(dimethylamino)benzophenone, evidence for exciplex formation has been obtained.

Synthesis of chiral organotin reagents: synthesis of enantiomerically enriched bicyclo[2.2.1]hept-2-yl tin hydrides from camphor. X-Ray crystal structures of (dimethyl)[(1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]tin chloride and methyl(phenyl)bis[(1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]stannane

2-Iodo-1,7,7-trimethylbicyclo[2.2.1]hept-2-ene 27 was prepared in two steps from camphor 23. Halogen–metal exchange using butyllithium followed by addition of the appropriate tin halide gave the corresponding bicyclo[2.2.1]hept-2-en-2-ylstannanes 26, 35–38 and the (diphenyl)bis[1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl]stannane 48. Reduction of the 1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-ylstannanes 35–38 using diimide took place predominantly from the exo-face to give the endo-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylstannanes 18, 43–45, endo–exo = ca. 80 ∶ 20 in all cases. The methyl(phenyl)bis[endo-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]stannane 51 was prepared from the diphenyl(methyl)[endo-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]stannane 40 by selective removal of one of the phenyl groups using iodine to give the dialkyl(phenyl)tin iodide 49 which was treated with the alkenyllithium reagent generated from the vinyl iodide 27 to give the bicyclo[2.2.1]hept-2-en-2-yl(dialkyl)phenylstannane 50, as a mixture of epimers at the tin. Reduction using diimide then gave the methyl(phenyl)bis[endo-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]stannane 51 whose structure was established by X-ray crystallography. The major (trimethyl)[1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]stannane 39 was shown to be the endo-isomer by an X-ray crystal structure determination of the tin chloride 46 prepared by treatment of the trimethylstannane 39 with tin tetrachloride. The configurations of the other stannanes 40–42 were established by analogy and by comparison of their 1H NMR spectra with those of 39. The dimethyl[1-dimethylaminomethyl-7,7-dimethylbicyclo[2.2.1]hept-2-enyl](phenyl)stannane 56 was similarly prepared from the parent ketone 52. The stannanes 41/44 and 51 were converted into the tin hydrides 59 and 61, but these gave only very modest enantiomeric excesses when used to reduce the bromoketone 62.

EPR investigation of persistent radicals produced from the photolysis of dibenzyl ketones adsorbed on ZSM-5 zeolites.

Photolysis of ketones (1, 1-oMe, 2, 2-oMe, 3, and 4) adsorbed on ZSM-5 zeolites produces persistent carbon-centered radicals that can be readily observed by conventional steady-state EPR spectroscopy. The radicals are persistent for time periods of seconds to many hours depending on the supramolecular structure of the initial radical@zeolite complex and the diffusion and reaction dynamics of radicals produced by photolysis. The structures of the persistent radicals responsible for the observed EPR spectra are determined by a combination of alternate methods of generation of the same radical, by deuterium substitution, and by spectral simulation. A clear requirement for persistence is that the radicals produced by photolysis must either separate and diffuse from the external to the internal surface or be generated within the internal surface and separate and diffuse apart. The persistence of radicals located on the internal surface is the result of inhibition of radical-radical reactions. Radicals that are produced on the external surface and whose molecular structure prevents diffusion into the internal surface are transient because radical-radical reactions occur rapidly on the external surface. The reactions of the persistent radicals with oxygen and nitric oxide were directly studied in situ by EPR analysis. In the case of reaction with oxygen, persistent peroxy radicals are formed in high yield. The addition of nitric oxide scavenges persistent radicals and leads initially to a diamagnetic nitroso compound, which is transformed into a persistent nitroxide radical by further photolysis. The influence of variation of radical structure on transience/persistence is discussed and correlated with supramolecular structure and reactivity of the radicals and their parent ketones.

Bisubstrate ketone analogues as serotonin N-acetyltransferase inhibitors.

Serotonin N-acetyltransferase, also called the melatonin rhythm enzyme, is thought to play an important regulatory role in circadian rhythm in animals and people. A series of analogues were synthesized in which indole and coenzyme A were linked via ketone tethers as designed inhibitors of this enzyme. These compounds were tested against purified serotonin N-acetyltransferase. The parent ketone compound was found to be as potent as an amide linked compound studied previously, suggesting that there are no key hydrogen bonds to the nitrogen atom of the corresponding substrate necessary for tight inhibition. Reduction of the parent ketone afforded the diastereomeric carbinol mixture which showed reduced inhibitory potency, arguing against tetrahedral analogue mimicry as an important inhibitory theme. Several conformationally constrained ketone analogues were synthesized and investigated, and the results indicated that directing the orientation of the two substrates within the bisubstrate system could be used to maximize enzyme inhibition.

Selective deoximation using alumina supported potassium permanganate

Ketoximes are converted to the parent ketones in good yields when treated with potassium permanganate supported on neutral alumina (ASPP). An optimized procedure has been developed, the simple work-up minimizes loss of product and oximes have been selectively oxidized in the presence of alkenes.

Triplet State of O-Acyloximes Studied by Time-Resolved Absorption Spectroscopy

Abstract Triplet states of O-acyloximes were studied for the first time by means of laser absorption spectroscopy. Energy transfer experiments showed that the acyl moiety has no effect on the triplet energy, which depends only on the ketone oxime part. It was observed that the difference between the triplet energy of the parent ketone and that of the oxime varies, depending on the oxime structure. This behaviour is explained on the basis of a non-vertical character of the energy transfer reaction.

Femtosecond Dynamics of Norrish Type-II Reactions: Nonconcerted Hydrogen-Transfer and Diradical Intermediacy.

Norrish type-II and McLafferty rearrangements, which both involve an intramolecular transfer of a gamma H atom, can be differentiated on the femtosecond time scale. The McLafferty rearrangement results in ion fragmentation of the parent ketone, whereas the Norrish type-II reaction leads to a diradical species, which then either cyclizes or fragments (see scheme). For Norrish type-II reactions, the reaction time for the transfer of the hydrogen atom is within 70 - 90 fs, and the lifetime of the diradical intermediate is in the range of 400 - 700 ps at the total energy studied.

Chiral overcrowded alkenes; asymmetric synthesis of (3S,3'S)-(M, M)-(E)-(+)-1,1',2,2',3,3',4,4'-octahydro-3,3',7,7'-tetramethyl-4, 4'-biphenanthrylidenes.

An asymmetric synthesis route towards (3S,3'S)-(M,M)-(E)-(+)-1,1',2, 2',3,3',4,4'-octahydro-3,3',7,7'-tetramethyl-4,4'-biphenanthrylidene was developed using the Evans procedure as a key step. The absolute configurations of the title compound and of its parent ketone were determined by CD spectroscopy and could be correlated with the stereochemical results of the asymmetric alkylation. Furthermore, a comparison was made with the known (3R,3'R)-(P,P)-(E)-(-)-1,1',2,2', 3,3',4,4'-octahydro-3,3',7,7'-dimethyl-4,4'-biphenanthrylidene. Finally, the X-ray crystallographic analysis of (3S,3'S)-(M, M)-(E)-(+)-1,1',2,2',3,3',4,4'-octahydro-3,3',7,7'-tetramethyl-4, 4'-biphenanthrylidene is presented.

Extreme thermal stability of disodium 9-fluorenone dianion as a practical indicator for the preparation of absolute THF

The fact that the lifetime of the disodium 9-fluorenone dianion is longer than that of the corresponding benzophenone dianion in refluxing THF for more than several months, which was proved by their 1H NMR analyses and also by the isolated yields of their oxidation products (parent ketones), strongly suggests using 9-fluorenone as an excellent indicator for the preparation of absolute THF.

Trimethylammonium Chlorochromate Adsorbed on Alumina: An Efficient and Convenient Reagent for the Oxidative Cleavage of 4-Phenylsemicarbazones and Semicarbazones to Their Parent Carbonyl Compounds

Deprotection of 4-phenylsemicarbazones and semicarbazones to their parent aldehydes and ketones in high yields has been carried out by using trimethylammonium chlorochromate adsorbed on alumina as selective oxidant under mild conditions.

Fotólise no estado estacionário e com pulso de laser de 1-benzociclanonas e de seus derivados <FONT FACE=Symbol>a</font>,<FONT FACE=Symbol>a</font> -dimetilados

Laser excitation of 0.01 M solutions of 1-indanone (Ia), 1-tetralone (Ib), 1-benzosuberone (Ic), and their a,a -dimethyl derivatives IIa-c, respectively, in benzene, produced transients with maximum absorption at 425 nm, and lifetimes ranging from 62 ns (IIa) to 5.5ms (Ic). Quenching studies using well known triplet quenchers such as 1,3-cyclohexadiene and oxygen demonstrated the triplet nature of these transients. In the presence of hydrogen donors, such as 2-propanol, the triplet state decay of the ketones Ia-c leads to the formation of the corresponding ketyl radicals, i.e. IIIa-c, which show absorption spectra very similar to the parent ketone, with lmax at 430 nm and lifetime in excess of 20 ms. Steady state irradiations show that the a,a -dimethyl ketones IIa and IIc form ortho-alkyl benzaldehydes probably derived from an initial a-cleavage of the corresponding triplet excited states.

The Cleavage of p-Nitrophenylhydrazones and Semicarbazones with Ammonium Chlorochromate Adsorbed on Alumina Under Non-Aqueous Conditions

Deprotection of p-nitrophenylhydrazones and semicarbazones to their parent aldehydes and ketones in good yields has been carried out by using ammonium chlorochromate adsorbed on alumina under mild conditions.

Regioselective Functionalization. 7.1 Unexpected Preferences for Bridgehead Migration in Schmidt Rearrangement Syntheses of Novel 2,6-Diazabicyclo[3.2.x]alkan-3-ones (x = 1−3)

Regioselective syntheses of 2,6-diazabicyclo[3.2.x]alkan-3-ones (x = 1−3) 34 by insertion of nitrogen next to the bridgehead (BH) of 2-azabicyclo[2.2.x]alkanones 32 with hydroxylamine-O-sulfonic acid are described. The ketones 32 under Schmidt reaction conditions (HN3/H2SO4) afford major amounts of BH migrated lactams 34 but also, when x = 2 or 3, the methylene (M) migrated lactams, 3,6-diazabicycl[3.2.x]alkan-2-ones 37. The present N-insertion reactions favoring BH migration with azabicyclic ketones contrast markedly with reactions of the related carbocycles 1a,b, which give only methylene migrated lactams 2a,b with HN3/H2SO4. Schmidt reactions of 3-anti/syn-methyl- and 3-anti-phenyl-2-azabicyclo[2.2.2]octan-5-ones 17, 20, and 23 (64:36 ± 9, BH:M) follow the reaction pattern of the parent ketone 14, but the 3-syn-phenyl ketone 26 gives major (65%) methylene migration. The results offer insights into the BH vs M migration dichotomy for the Beckmann and Schmidt reactions of bridged bicyclic ketones.

Oxidative Deoximation to Their Parent Carbonyl Compounds with Ammonium Chlorochromate Adsorbed on Alumina

A convenient method for the oxidative cleavage of oximes to their parent aldehydes and ketones with ammonium chlorochromate adsorbed on alumina is described

Crystal Structure of the E-2,4-Dinitrophenylhydrazone of 2-Acetyl-3-phenyl-5-methylfuran

The molecular structure of the title E-(syn)-2,4-dinitrophenylhydrazone (DNPH) has been determined and compared with that of the known parent ketone. Semiempirical (AM1, PM3) and molecular mechanics (MM+, Sybyl) calculations gave inconclusive results regarding the possible configurations (syn versus anti) and conformations (s-cis versus s-trans). In the crystal the title molecule is almost planar in an s-trans conformation with the phenyl ring twisted by 30.0° out of the furan plane. Thus, the present DNPH, in the syn configuration, mimics very well the conformation of the parent crystalline ketone. The previous assignment based on solution data of this DNPH as anti is incorrect. It is thus shown that due to the strong intramolecular hydrogen bond NH⋯O2N (ortho) within the DNPH part, the syn-anti DNPH formation is not affected by the putative hydrogen bond to the furanic oxygen atom.