110-87-2

Enamines and enol ethers are versatile synthons for chemical synthesis. While several methods have been developed to access such molecules, prefunctionalized starting materials are usually required, and direct desaturation methods remain rare. Herein, we report direct desaturation reactions of N-protected cyclic amines and cyclic ethers using a mild I(III) oxidant, PhI(OAc)2, and an electron-deficient manganese pentafluorophenylporphyrin catalyst, Mn(TPFPP)Cl. This system displays high efficiency for α,β-desaturation of various cyclic amines and ethers. Mechanistic probes suggest that the desaturation reaction occurs via an initial α-C-H hydroxylation pathway, which serves to protect the product from overoxidation.

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In the presence of a catalytic amount of NidppeCl2, 2-methoxy- 5,6-dihydro-2H-pyran reacts with primary Grignard reagents to give the corresponding 2-n.alkyl-5,6-dihydro-2H-pyrans in satisfactory yields.

The products formed in 2-methoxytetrahydropyran elimination reaction in the gas phase are 3, 4-dihydro-2H-pyran and methanol. The kinetic study was carried out in a static system, with the vessels deactivated with allyl bromide, and the presence of the free radical suppressor toluene. Temperature and pressure ranges were 400-450 °C and 25-83 Torr, respectively. The process is homogeneous, unimolecular, and follows a first-order rate law. The observed rate coefficient is represented by the following equation: log k (s-1) = (13.95 ± 0.15) - (223.1 ± 2.1) (kJ mol-1) (2.303RT)-1. The reactant exists mainly in two low energy chair-like conformations, with the 2-methoxy group in axial or equatorial position. However, the transition state (TS) for the elimination of the two conformers is the same. Theoretical calculations of this reaction were carried for two possible mechanisms from these conformations by using DFT functionals B3LYP, MPW1PW91, and PBE with the basis set 6-31G(d,p) and 6-31G++(d,p). The calculation results demonstrate that 2-methoxytetrahydropyran exists mainly in two conformations, with the 2-methoy group in axial or equatorial position, that are thermal in equilibrium. The average thermodynamic and kinetic parameters, taking into account the populations of the conformers in the equilibrium, are in good agreement with experimental values at B3LYP/6-31++(d,p) level of theory. Copyright

Vapor-phase synthesis of 3,4-2H-dihydropyran (DHP) from tetrahydrofurfuryl alcohol (THFA) was investigated over acidic catalysts modified with transition metals. Catalytic activity of alumina was seriously deactivated in the reaction of THFA in nitrogen at 300 °C although the initial activity was high. Tetragonal ZrO2 showed the catalytic activity to produce DHP at 350 °C. Alumina modified with Cu exhibits stable catalytic activity with high selectivity to DHP under hydrogen flow conditions, and the optimum activity was obtained at CuO contents of 5-10 wt.%: the selectivity to DHP was as high as 85%. Prior to the reaction, CuO was reduced to metallic Cu, which probably works as a product remover together with hydrogen to prevent coke formation. The reaction pathway from THFA to DHP was discussed: it is speculated that THFA is initially rearranged into 2-hydroxytetrahydropyran, which rapidly dehydrated to DHP.

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A series of MeOx-modified CeO2 (CeO2-MnOx, CeO2-ZnO, CeO2-MgO, CeO2-CaO, and CeO2-Na2O) catalysts were prepared by the impregnation of CeO2 with corresponding metal nitrates. Acidity and oxidation state of cerium were investigated on both oxidized and reduced catalysts by employing Fourier Transform Infrared spectroscopy (FTIR) on adsorbed pyridine and in situ H2-Temperature Programmed Reduction/X-ray Absorption Spectroscopy (H2-TPR/XAS) techniques, respectively. Metal oxide addition tended to alter both type and number of acid sites on ceria. EXAFS data showed a significant difference in NCe-O between unmodified and CeO2-MeOx, suggesting that added MeOx interferes with vacancy formation on ceria during reduction. In comparison with air-pretreated samples, H2-pretreated ones under similar conversion of 1,5 pentanediol exhibited a higher selectivity towards linear alcohols. Alcohol conversion found to correlate with total acidity (i.e., Br?nsted and Lewis). CeO2 benefited from the addition of alkali (Na) or alkaline earth metals (Mg, Ca) by producing unsaturated alcohols.

A method of making 1,5-pentanediol from tetrahydrofurfural alcohol. The method includes the steps of dehydrating tetrahydrofurfural alcohol (THFA) to dihydropyran (DHP); hydrating at least a portion of the DHP to 2-hydroxy-tetrahydropyran (2-HY-THP) in the presence of a solid acid catalyst; and hydrogenating at least a portion of the 2-HY-THP to 1,5-pentanediol. The method can be conducted entirely in the absence of noble metal catalysts.

The gas-phase elimination kinetics of tetrahydropyranyl phenoxy ethers: 2-phenoxytetrahydro-2H-pyran, 2-(4-methoxyphenoxy)tetrahydro-2H-pyran, and 2-(4-tert-butylphenoxy)tetrahydro-2H-pyran were determined in a static system, with the vessels deactivated with allyl bromide, and in the presence of the free radical inhibitor toluene. The working temperature and pressure were 330 to 390°C and 25 to 89?Torr, respectively. The reactions yielded DHP and the corresponding 4-substituted phenol. The eliminations are homogeneous, unimolecular, and satisfy a first-order rate law. The Arrhenius equations for decompositions were found as follows: 2-phenoxytetrahydro-2H-pyran log k1 (s?1)?=?(14.18?±?0.21)???(211.6?±?0.4)?kJ?mol?1 (2.303 RT)?1 2-(4-methoxyphenoxy)tetrahydro-2H-pyran log k1 (s?1)?=?(14.11?±?0.18)???(203.6?±?0.3)?kJ?mol?1 (2.303 RT)?1 2-(4-tert-butylphenoxy)tetrahydro-2H-pyran log k1 (s?1)?=?(14.08?±?0.08)???(205.9?±?1.0)?kJ?mol?1 (2.303 RT)?1. The analysis of kinetic and thermodynamic parameters for thermal elimination of 2-(4-substituted-phenoxy)tetrahydro-2H-pyranes suggests that the reaction proceeds via 4-member cyclic transition state. The results obtained confirm a slight increase of rate constant with increasing electron donating ability groups in the phenoxy ring. The pyran hydrogen abstraction by the oxygen of the phenoxy group appears to be the determinant factor in the reaction rate.

A method of making 1,5-pentanediol from tetrahydrofurfural alcohol. The method includes the steps of dehydrating tetrahydrofurfural alcohol (THFA) to dihydropyran (DHP); hydrating at least a portion of the DHP to 2-hydroxy-tetrahydropyran (2-HY-THP) in the absence of homogeneous acid; and hydrogenating at least a portion of the 2-HY-THP to 1,5-pentanediol. The method can be conducted entirely in the absence of noble metal catalysts.

PROBLEM TO BE SOLVED: To provide a method of producing 3,4-dihydro-2H-pyran at a high raw material conversion rate and with excellent selection rate, while maintaining high catalyst activity, in production of 3,4-dihydro-2H-pyran from a raw material tetrahydrofurfuryl alcohol due to a gas phase reaction that uses a solid catalyst. SOLUTION: A production method of 3,4-dihydro-2H-pyran for obtaining 3,4-dihydro-2H-pyran by making a tetrahydrofurfuryl alcohol gas contact with a catalyst under presence of hydrogen gas is a method of producing 3,4-dihydro-2H-pyran in which the catalyst is a catalyst in which ruthenium is supported by a metal oxide. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT

Catalytic systems containing Rh(acac)(CO)2 or Rh/PAA (PAA?=?polyacrylic acid) and hydrophobic phosphine (PPh3) were used in the hydroformylation of diolefins, alkynes, and unsaturated alcohols under solventless and “on water” conditions. The total yield of dialdehydes obtained from 1,5-hexadiene and 1,7-octadiene reached 99%, and regioselectivity towards linear dialdehydes was higher in the “on water” system. The tandem hydroformylation-hydrogenation of phenylacetylene led to the formation of saturated aldehydes (3-phenylpropanal and 2-phenylpropanal) at 98% conversion with a good regioselectivity towards the linear aldehyde in the “on water” reaction. In contrast, solventless conditions appeared better in the hydroformylation of 1-propen-3-ol. 4-Hydroxybutanal, formed in this reaction with an excellent selectivity, was next transformed to tetrahydrofuran-2-ol via a ring-closure process. Cyclic products were also obtained in hydroformylation of 1-buten-3-ol. In reaction of undec-1-ol and 2-allylphenol linear aldehydes were formed with the yield 69–87%. The hydroformylation of 3-buten-1-ol performed under “on water” conditions showed very good regioselectivity towards a linear aldehyde, 5-hydroxypentanal. Further cyclization of the aldehyde to tetrahydropyran-2-ol was observed.

The present invention relates to a process for the preparation of 2,3-dihydropyran (DHP, CAS [110-87-2]) and its use in industrial chemistry.

The present invention relates to a process for producing 2,3-dihydropyran (DHP), comprising contacting tetrahydrofurfuryl alcohol (THFA) entrained in a carrier gas with a catalyst comprising aluminium oxide (Al2O3), wherein the carrier gas is water vapour.

The new ruthenium complex [Ru(N3P)(OAc)][BPh4] (4), in which N3P is the N,P mixed tetradentate ligand N,N-bis[(pyridin-2-yl)methyl]-[2(diphenylphosphino)phenyl]methanamine was synthesized. The complex was found to be catalytically active for the endo cycloisomerization of alkynols. The catalytic reactions can be used to synthesize five-, six-, and seven-membered endo-cyclic enol ethers in good to excellent yields. A catalytic cycle involving a vinylidene intermediate was proposed for the catalytic reactions. Treatment of complex 4 with PhC≡CH and H2O gave the alkyl complex [Ru(CH2PhJ(CO)(N 3P)][BPh4] (30), which supports the assumption that the catalytic reactions involve addition of a hydroxyl group to the C=C bond of vinylidene ligands.

PtCl2 effectively catalyzes the multistep reaction of N-methyl indole (1a) with pent-3-yn-1-ol (2a) in THF at room temperature for 2 h to give indole derivative 3a, which contains a five-membered cyclic ether group at C3 in 93 % yield. Under similar reaction conditions, various substituted N-methyl indoles 1b-h and indole (1i) reacted efficiently with 2 a to afford the corresponding indole derivatives 3b-h and 3i in 48-91 and 72 % yields. The results showed that N-methyl indoles with electron-donating substituents were more reactive affording higher product yields than those with electron-withdrawing groups. Likewise, various substituted but-3-yn-1-ols 2b-e and other longer chain alkynyl alcohols 2 f-i also underwent a cyclization-addition reaction with N-methyl indole (1a) to provide the corresponding cyclization-addition products 3j-m and 3a, 3j, and 3n-o in good to excellent yields. The present platinum-catalyzed cyclization-addition reaction can be further extended into N-methyl pyrrole. Mechanistically, the catalytic reaction proceeds by an intramolecular hydroalkoxylation of alkynyl alcohol to afford cyclic enol ether followed by the addition of the C-H bond of indole to the unsaturated moiety of cyclic enol ether providing the final product. Experimental evidence to support this proposed mechanism is provided.

Compounds inhibit memapsin 2 β-secretase activity and selectively inhibit memapsin 2 β-secretase activity relative to memapsin 1 β-secretase activity. The compounds are employed in methods to inhibit memapsin 2 β-secretase activity, in the treatment of Alzheimer's disease, in the inhibition of hydrolysis of a β-secretase site of a βamyloid precursor protein and to decrease β-amyloid protein in in vitro samples and in mammals. Proteins of memapsin 2 associated with compounds of the invention are crystallized.

a process for the preparation of indanones of the formula II from, indanones of the formula I or of indanones of the formula IIa from indanones of the formula Ia comprises reacting an indanone of the formula I or Ia with a coupling component.

The invention relates to fragrance precursors, In particular, the invention relates to the use of several classes of compounds which may act as fragrance precursors, e,g., in cosmetic products such as deodorants and antiperspirants and in laundry products such as detergents and fabric softners. These compounds are odorless, but upon contacting the skin as example, in skin care compositions or in personal care compositions, produce fragrances. The compounds also produce fragrances when used in the presence of lipases, e.g. as used in (laundry) detergents, thus providing a prolongation of the fabric scenting effect. The compounds under consideration are compounds of the formula I: The substituents are defined in the specification.

A method for the preparation of hydroxythiol compounds by reacting a hydroxyl-protected halide compound having the structure:X-R-OPgwith magnesium in a Grignard-suitable solvent to form a hydroxyl-protected magnesium halide compound, wherein R is selected from substituted or unsubstituted aliphatic radicals, substituted or unsubstituted cyclic aliphatic radicals, substituted or unsubstituted aromatic radicals, substituted or unsubstituted araliphatic radicals and substituted or unsubstituted heterocyclic radicals; Pg is a protecting group; and X is selected from the group consisting of F, Cl, Br and I; then reacting said hydroxyl-protected magnesium halide compound with sulfur in the Grignard-suitable solvent to form a hydroxyl-protected thiomagnesium halide compound; and hydrolyzing the protected hydroxyl group to form a hydroxythiomagnesium halide compound and converting the thiomagnesium halide to a thiol; wherein the protecting group is selected so that species formed by the de-protection of the protecting group are inert toward thiols, or the method further includes the step of removing the protecting group species formed by de-protection of the hydroxyl group from the reaction mixture before converting the thiomagnesium halide to a thiol.

This invention relates to compositions, compounds and methods for lightening skin, using active compounds having the structure: STR1 wherein: (i) each X is, independently, selected from the group consisting of halo, alkyl, substituted alkyl, aryl, OR, OCOR, COR, CONRR COOR, CN, SR, SOR, SO2 R, SO3 R and NRR, wherein X is other than hydroxy, amino and thio, if this X is attached ortho to the phenol hydroxy; (ii) m is an integer from 0 to 4; (iii) each R' and each R" is, independently, selected from the group consisting of hydrogen, halo, alkyl, substituted alkyl, aryl, OR, OCOR, OCRROR, COR, CR(OR)OR, CONRR, COOR, CRROR, CN, SR, and NRR; wherein halo, when it appears, is other than geminal to a hydroxy, NH2, or SH; (iv) R'" is alkyl or substituted alkyl; wherein when R'" is present, wherein when R'" is present and R' is also hydrogen, R" is other than hydrogen, hydroxy, halo, thio, cyano and amino; (v) each R is, independently, selected from the group consisting of hydrogen, alkyl, substituted alkyl and aryl; (vi) n is an integer from 1 to about 5, wherein at least one carbon in (C)n has other than alkyl or hydroxy as a substituent and (C)n adjacent to Z has other than amino, SH, CN or hydroxy as R'; (vii) Z is selected from the group consisting of O, NR, S, SO, SO2, PO2 R and POR; (viii) wherein any carbon, when disubstituted, having as one substituent selected from the group consisting of hydroxy, amino, cyano and thiol, has the other substituent selected from the group consisting of hydrogen, alkyl, and aryl, whether this substituent is R' or R"; and to pharmaceutically acceptable salts of these compounds, stereoisomers and enantiomers thereof free from or mixed with other enantiomers or stereoisomers; and such compounds in compositions with a pharmaceutically-acceptable carrier thereof comprising a safe and effective amount of a subject skin lightening active.

The conversions of furan, di- and tetrahydrofuran, and di- and tetrahydropyran on a molybdenum catalyst in a hydrogen atmosphere have been investigated. The studied cyclic systems readily undergo mutual conversions at 125-215°C and also undergo a hydrogenation-dehydrogenation reaction. Expansion of the unsubstituted furan rings to pyran without the introduction into the reaction medium of components capable of generating methyl radicals are described by us for the first time.

The 1,4-oxathiine-S-oxides 6 when heated at 60 deg C in CHCl3 undergo a retro Diels-Alder reaction with generation of α,α'-dioxosulfine 8.This reactive intermediate can be trapped by electron rich dienophiles as well as by dienes.In both cases the cycloaddition reactions show interesting stereoselective features.

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The invention provides a process for the preparation of 5,6-dihydro-2H-pyran derivatives, wherein an aldehyde of formula I: STR1 wherein R1 represents an alkyl, cycloalkyl, aralkyl, alkaryl or aryl group having at most 15 carbon atoms and a diene of formula II: STR2 wherein R2 and R3 represents a hydrogen atom or an alkyl group having 1-6 carbon atoms are reacted in a Diels-Alder-type reaction under the influence of an inorganic Lewis acid catalyst, producing a compound of formula III wherein R1 -R3 have the meaning given above. STR3 Preferably R1 represents a 1-6 carbon atom alkyl group, a phenyl group or an o-, m- or p-tolyl group. Isoprene or 2-methyl-1,3-pentadiene is preferably used as the diene. The preferred catalyst is AlCl3 or SnCl4 and an organic nitro compound may be used as the co-catalyst.

The chemoselective conversion of allyl and prop-2-ynyl acetals as well as ketals by reductive cleavage with catecholborane into the corresponding allyl and prop-2-ynyl ethers is described.

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Compounds of formula I STR1 wherein: R1 is hydrogen or hydroxy, and the methyl and hydroxy groups at 6- and 7-positions respectively can be either in α or β configuration, are useful in human therapy. Compounds I are prepared by methylation of the corresponding appropriately protected 7-keto-derivatives.

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Novel 7-hydroxyguanine compounds of the formula: STR1 wherein R is hydrogen atom, tetrahydropyranyl group or tetrahydrofuryl group, and R2 is hydrogen atom, tetrahydropyranyl group or tetrahydrofuryl group, provided that when R1 is hydrogen atom, R2 is tetrahydropyranyl group or tetrahydrofuryl group, and a salt thereof, which have excellent anti-tumor activity, process for preparing the compounds, and anti-tumor agent containing said compound as an active ingredient.

The gas phase basicity (GB) of dihydropyran 1 and dihydro-1,4-dioxin 2 is measured in equilibrium proton transfer reactions conducted in an ion cyclotron resonance spectrometer.GB(1) is found to be greater than GB(2) by 37 kJ mol-1, this difference parallels the lower reactivity of 2 observed in solution under acidic condition.Conclusion as to the favoured protonation of the C-C double bond, giving rise for both 1 and 2 to oxycarbonium cations, is drawn from comparison with analogous compounds and substantiated by molecular orbital calculations (MNDO) on the protonated structures.

A novel prostaglandin analogue of the formula: STR1 [wherein the symbol represents β-configuration, the dotted line ---------- represents α-configuration, and the double bond between C13 -C14 represents transconfiguration] and cyclodextrin clathrates thereof, and non-toxic salts thereof are useful for the treatment and/or prevention of diseases induced by platelet aggregation, such as thrombosis, or induced by cytodamage.

The stereochemical outcome of the sodium ring-scission of 2-substituted 3-halogenotetrahydro-pyrans and -furans, with 2-substitution represented by alkyl, alkenyl or aryl, is presented.Although the cis- and the trans-tetrahydropyran scissions are hyghly stereoselective for (E)-5-substituted pent-4-enol, this stereoselectivity breaks down when the 2-substituent is conformationally undiscriminating (deuterium) or has substantial anomeric effects (methoxy).Consideration of this, along with conformational data from the preceding paper, provides an explanation of the stereoselectivity of the tetrahydropyran scission.Evidence against a radical, and for a carbanion intermediate is presented and a common, very rapidly inverting, 3-carbanion is considered to be formed from either cis- or trans-stereoisomers.Ring scission is also rapid (the carbanion cannot be trapped), but less rapid than carbanion inversion, and takes place before the slower conformational inversion can occur so that the (E)/(Z)-nature of the unsaturated alcohol produced is controlled by the initial tetrahydropyran conformation.The unstereospecific nature of the ring scission of both cis- and trans-2-alkyl-3-chlorotetrahydrofurans is explained as a consequence of their existence in conformational equilibria. The high stereoselectivity of the ring scission of cis- and trans-3-chloro-2,3-dimethyltetrahydropyrans, and the poor stereoselectivity of the scission of 2-alkyl-3-chloro-2-methyltetrahydrpyrans, is explained; the reaction of sodium with 2-butyl-3,3-dichlorotetrahydropyran is considered.Using the ring-scission of 3-chlor-2-ethyltetrahydropyran, short syntheses of (+/-)-endo-brevicomin are described to illustrate the utility of β-halogen ether synthesis.

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2,3,4,5-Tetrahydrooxepin treated with either n-butyllithium or tert-butyllithium affords 7-lithio-2,3,4,5-tetrahydrooxepin.The question of allylic vs. vinylic deprotonation of cyclic vinyl ethers was examined by varying ring size and degree of unsaturation.Carbon-13 spectral data for the anions obtained from 2,5-dihydrofuran, 2,3-dihydrooxepin, and 2,3,4,5-tetrahydrooxepin are reported.In contrast to 2,3,4,5-tetrahydrooxepin, 2,3-dihydrooxepin undergoes allylic deprotonation, possibly as a result of a slightly larger C-C=C bond angle in the dihydrooxepin as compared to that of the tetrahydrooxepin.

This invention relates to 3-(phenyl/naphthyl)-benz[d]isothiazole-1,1-dioxides wherein the 3-phenyl or the 3-naphthyl group is substituted in the para position with hydroxy blocked with certain protecting groups. These compounds are useful as intermediates in the synthesis of certain 3,3-disubstituted-2,3-dihydrobenz[d]isothiazole-1,1-dioxide dyes which find utility, for example, as photographic optical filter agents and filter agent precursors.

This invention relates to 1-naphthol sulfam(na)phthaleins possessing a carbonyl moiety on the N atom of sulfam(na)phthalein ring, which compounds find utility, for example, as antihalation and filter dyes in photographic products and processes.

This invention relates to a method of synthesizing certain 3-(carbocyclic aryl)-3-(4'-OP-carbocyclic aryl)-2,3-dihydrobenz[d]isothiazole-1,1-dioxides (and -2,3-dihydronaphtho[1,8-de]-1,2-thiazine-1,1-dioxides) by reacting (a) a 4-OP-carbocyclic aryllithium compound wherein P is a protecting group and (b) a 3-(carbocyclic aryl)benz[d]isothiazole-1,1-dioxide wherein said 3-(carbocyclic aryl) moiety is other than a 3-(4'-OP-carbocyclic aryl) moiety to give (c) the corresponding 3-carbocyclic aryl)-3-(4'-OP-carbocyclic aryl)-2,3-dihydrobenz[d]isothiazole-1,1-dioxide. The -2,3-dihydronaphtho[1,8-de]-1,2-thiazine-1,1-dioxides are prepared in the same manner by reacting a 3-(carbocyclic aryl)naphtho[1,8-de]-1,2-thiazine-1,1-dioxide with said 4'-OP-carbocyclic aryllithium compound. In a further embodiment, the compounds synthesized according to the foregoing method are reacted with a carboxylic acid halide to give the corresponding 2-carbonyl-substituted 2,3-dihydrobenz[d]isothiazole-1,1-dioxide (or -2,3-dihydronaphtho[1,8-de]-1,2-thiazine-1,1-dioxides) followed by removing the protecting group, P, with weak acid to yield certain phenol and 1-naphthol sulfam(na)phthaleins useful, e.g., as optical filter agents and filter agent precursors in photography.