Oxygen-containing Substituents Research Articles

Debenzylation of Functionalized 4- and 5-Substituted 1,2,3-Triazoles

A range of 4- and 5-substituted N-benzyl-1,2,3-triazoles have been submitted to debenzylation using Pd/C and hydrogen in the presence of 1,1,2-trichloroethane. Triazoles with oxygen-containing substituents are efficiently debenzylated under these conditions. Triazoles with a phenyl or benzyl substituent on C4 or C5 are not debenzylated, whereas a pentyl-substituted derivative was readily debenzylated.

Synthesis and antitumour activity of β-hydroxyisovalerylshikonin analogues

A series of novel β-hydroxyisovalerylshikonin analogues bearing oxygen-containing substituents at the side-chain hydroxyl of shikonin were designed and synthesized. The cytotoxicities of these compounds were evaluated in vitro against multi-drug resistant (MDR) cell lines DU-145 and HeLa. Most compounds exhibited significant inhibitory activity on both cell lines. The structure–activity relationship showed the analogues with ether substituents displayed the most potent antitumour activity and selective cytotoxicity towards DU-145. Among the compounds with ether substituents, increasing the steric hindrance in the carbon bearing β-hydroxyl or replace the β-hydroxyl with acetoxy or methoxy would lead to the decline of cytotoxicity.

Kadsutherins A—C: Three New Dibenzocyclooctane Lignans from the Stems of Kadsura Species

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Chemotopic representations of aromatic odorants in the rat olfactory bulb

Our laboratory has characterized spatial patterns of evoked neural activity across the entire glomerular layer of the rat olfactory bulb using primarily aliphatic odorants that differ systematically in functional groups and hydrocarbon structures. To represent more fully the true range of odorant chemistry, we investigated aromatic compounds, which have a more rigid molecular structure than most aliphatic compounds and are particularly salient olfactory stimuli for humans. We first investigated glomerular patterns of 2-deoxyglucose uptake in response to aromatic compounds that differ in the nature and position of their functional groups (e.g., xylenes, trimethylbenzenes, tolualdehydes, benzaldehydes, methyl toluates, and anisaldehydes). We also studied the effects of systematic increases in the number and length of alkyl substituents. We found that most aromatic compounds activated glomeruli in the dorsal part of the bulb. Within this general area, aromatic odorants with oxygen-containing substituents favored activation of more rostral regions, and aromatic hydrocarbons activated more posterior regions. The nature of substituents greatly affected the pattern of glomerular activation, whereas isomers differing in substitution position evoked very similar overall patterns. These relationships between the structure of aromatic compounds and their spatial representation in the bulb are contrasted with our previous findings with aliphatic odorants.

Carbon−Carbon Bond Formation Promoted by Adjacent Metal Centers: Regioselective Alkyne Insertions into a “Rh(μ-CH2)Ru” Moiety Yielding C3- and C5-Bridged Fragments

The heterobinuclear complex [RhRu(CO)3(μ-CH2)(dppm)2][CF3SO3] (2) (dppm = Ph2PCH2PPh2), generated in situ from the tetracarbonyl precursor, reacts with the alkynes, dimethyl acetylenedicarboxylate, hexafluoro-2-butyne, and diethyl acetylenedicarboxylate to give the C3-bridged products [RhRu(CO)3(μ-η1:η1-C(R)C(R)CH2)(dppm)2][CF3SO3] (R = CO2CH3 (3), CF3 (4), CO2CH2CH3 (5)), in which the alkynes have inserted into the Rh−C bond of the bridging methylene group. Compound 2 also reacts with 2-butyn-1-al diethylacetal and 2-butyn-1-ol, producing the insertion products [RhRu(CO)3(μ-η1:η1-C(CH3)C(R)CH2)(dppm)2][CF3SO3] (R = CH(OEt)2 (6), CH2OH (7)) analogous to compounds 3−5. The regiochemistry of alkyne insertion in both cases has been established by 2-D NMR spectroscopy; the methyl substituent is adjacent to Rh, and the oxygen-containing substituent is adjacent to the methylene group. Attempts to generate an isomer of 3 by the reverse sequence of methylene insertion into the Rh−C bond of the alkyne-bridged species [RhRu(CO)3(μ-η1:η1-C(CO2CH3)C(CO2CH3))(dppm)2][X] (X = BF4 (8a), CF3SO3 (8b)) failed with no reaction occurring, although reaction of the dicarbonyl analogue, [RhRu(OSO2CF3)(CO)2(μ-η1:η1-C(CO2CH3)C(CO2CH3))(dppm)2], with CH2N2 results in methylene insertion into the Rh−Ru bond to give [RhRu(OSO2CF3)(CO)2(μ-CH2)(μ-η1:η1-C(CO2CH3)C(CO2CH3))(dppm)2] (10). Reaction of 3 with trimethylamine-N-oxide results in loss of a carbonyl and a rearrangement of the C3-bridged group, affording [RhRu(CO)2(μ-η1:η3-CHC(CO2CH3)CH(CO2CH3))(dppm)2][CF3SO3] (11). Propargyl alcohol reacts with 2, affording a double-insertion product [RhRu(CO)2(μ-η2:η4-CHC(CH2OH)CHC(CH2OH)CH2)(dppm)2][CF3SO3] (12) with incorporation of two propargyl alcohol units in a head-to-tail arrangement. The structures of compounds 4, 8a, and 12 were determined by X-ray methods.

Oxygenated analogues of gorgosterol and ergosterol from the soft coral Capnella lacertiliensis.

From the dichloromethane solubles of Capnella lacertiliensis five new sterols were isolated that are highly functionalized with oxygen-containing substituents: 12beta-acetoxy-7alpha-hydroxygorgosterol (1), 12beta-acetoxy-7alpha,19-dihydroxygorgosterol (2), 12beta-acetoxyergost-5-ene-3beta,23-diol (4), 12beta-acetoxyergost-5-ene-3beta,11beta,16-triol (5), and 11beta-acetoxyergost-5-ene-3beta,12beta,16-triol (6). The structures of all compounds were deduced from interpretation of their spectroscopic data, mainly 1D and 2D NMR spectra and HREIMS. Biological activities of the isolates were assessed, and all were found to be weakly antifungal. Compounds 5 and 6 were also found to have weak tyrosine kinase p56(lck)() (TK) inhibitory activity at the 200 microgram/mL level.

ChemInform Abstract: Synthesis of Modified Vitamin D Precursors.

Modified vitamin D precursors with oxygen-containing substituents at various positions in the side-chain were obtained using previously synthesized 20-isoxazolin-3′-yl-and 20-isoxazolin-5′-ylsteroids.

Functional poly(1,4-ketone)s with pendant hydroxy moieties, 1. Pd(II)-catalyzed alternating copolymerization of carbon monoxide and allylbenzene derivatives

Functional poly(1,4-ketone)s were prepared by alternating copolymerization of carbon monoxide with substituted allylbenzenes, namely 2-allylphenol 1, 2-allyl-4-methylphenol 2, 2-allyl-6-methylphenol 3, 2-allylmethoxybenzene 4, 2-allylethoxybenzene 5, 2-allylacetoxybenzene 6 and 4-allylmethoxybenzene 7. The dicationic Pd(II) bis(phosphine) complex [Pd(DPPP)(CH3CN)2] (BF4)2 10 [DPPP = 1,3-bis(diphenylphosphino)propane] was used as the catalyst precursor. Optimum results occurred with monomers that bear oxygen-containing substituents located in ortho-position to the allyl group. Copolymers derived from phenolic monomers structurally differ from their protected analogues because they predominantly display ketalic character due to nucleophilic attack of the OH groups towards neighbored keto moieties. Pendant hydroxy moieties of functional poly(1,4-ketone)s were reacted with chlorides and anhydrides of carboxylic acids to form the corresponding esters as a model reaction for grafting processes. Furthermore, isocyanates were used in terms of post-polymerization functionalization.

Functional poly(1,4-ketone)s with pendant hydroxy moieties, 1. Pd(II)-catalyzed alternating copolymerization of carbon monoxide and allylbenzene derivatives

Functional poly(1,4-ketone)s were prepared by alternating copolymerization of carbon monoxide with substituted allylbenzenes, namely 2-allylphenol 1. 2-allyl-4-methylphenol 2. 2-allyl-6-methylphenol 3. 2-allylmethoxybenzene 4. 2-allylethoxybenzene 7. The dicationic Pd(II) bis(phosphine) complex [Pd(DPPP)(CH 3 CN) 2 ] (BF 4 ) 2 10 [DDP = 1,3-bis-diphenylphosphino)propane] was used as the catalyst precursor. Optimum results occurred with monomers that bear oxygen-containing substituents located in ortho-position to the allyl group. Copolymers derived from henolic monomers structurally differ from their protected analogues because they predominantly display ketalic character due to nucleophilic attack of the OH groups towards neighbored keto moieties. Pendant hydroxy moieties of functional poly (1,4-ketone)s were reacted ith chlorides and anhydrides of carboxylic acids to form the corresponding esters as a model reaction for grafting processes. Furthermore, isocyanates were used in terms of post-polymerization functionalization. Graph. Dependence of molecular weight and copolymer yield on the acivator concentration in the alternating copolymerization of CO and 1.

Synthesis of modified vitamin D precursors

Modified vitamin D precursors with oxygen-containing substituents at various positions in the side-chain were obtained using previously synthesized 20-isoxazolin-3′-yl-and 20-isoxazolin-5′-ylsteroids.

Intramolecular and intermolecular geometry of thiophenes with oxygen-containing substituents.

The intramolecular and intermolecular geometries of six thiophenes carrying oxygen-containing substituents have been determined. Crystals of 2-methoxythiophene and 3-methoxythiophene were grown in situ on a diffractometer from liquid samples. The 2-methoxy group introduces significant distortions to the thiophene nucleus and each molecule participates in four S.O contacts leading to an infinite bilayer. The extended structure of 3-methoxythiophene comprises zigzag chains of molecules linked by S.O contacts. Molecules of 2-acetyl-3-methoxythiophene are arranged in pairs about inversion centres, with ring centroids 3.835 Å apart. 5-Cyano-3-hydroxythiophene adopts the hydroxythiophene tautomeric form which allows conjugation between the S atom and the nitrile group: O-H.N hydrogen bonding leads to chains which are cross-linked by S.O contacts to give infinite two-dimensional layers. 5-(Methylthio)thiophen-3(2H)-one exists exclusively as the thiophen-3(2H)-one form in the solid state, allowing maximum conjugative interaction of both the ring heteroatom and the substituent with the carbonyl group: each molecule is linked to two of its neighbours through pairwise C-H.O interactions, forming ribbons. Spiro[cyclohexane-1,2'-2',3'-dihydrothiophen]-3'-one crystallizes with four independent molecules in the asymmetric unit with only minor differences between these: the five- and six-membered rings in each molecule are approximately orthogonal and C-H.O hydrogen bonding generates chains. The last two structures differ from the others in that they lack a fully aromatic thiophene system.

The ring-opening metathesis polymerization of dicyclopentadiene with titanocene complexes

The ring-opening metathesis polymerization of dicyclopentadiene with dimethyltitanocene and in situ prepared substituted dimethyltitanocenes was studied. The results showed that at low concentration dimethyltitanocene catalyzed the polymerization of dicyclopentadiene to give linear polymer at 70–90°C and that the introduction of oxygen-containing substituents on cyclopentadienyl rings decreased catalytic activity due to a steric effect.

Liquid Chromatography Analysis of Carbonyl (2,4-Dinitrophenyl)hydrazones with Detection by Diode Array Ultraviolet Spectroscopy and by Atmospheric Pressure Negative Chemical Ionization Mass Spectrometry

The (2,4-dinitrophenyl)hydrazones of carbonyls are separated by liquid chromatography and detected by ultraviolet spectroscopy (diode array detector) and by atmospheric pressure negative chemical ionization mass spectrometry. Results are presented for 78 carbonyls including 18 1-alkanals (from formaldehyde to octadecanal), 16 other saturated aliphatic carbonyls (5 C(4)-C(7) aldehydes and 11 C(3)-C(9) ketones), 16 unsaturated aliphatic carbonyls (9 C(3)-C(11) aldehydes and 7 C(4)-C(9) ketones), 13 aromatic carbonyls (including hydroxy- and/or methoxy-substituted compounds), 10 C(2)-C(10) aliphatic dicarbonyls, 3 aliphatic carbonyl esters, and 2 other carbonyls. Isomers were observed for α,β-unsaturated ketones and saturated carbonyls that bear other oxygen-containing substituents, e.g. methoxyacetone, 2-furaldehyde, and the 3 carbonyl esters. For all but two of the carbonyls studied, the base peak in the negative APCI mass spectrum was the M - 1 ion (NO(2))(2)C(6)H(3)NN [Formula: see text] CR(1)R(2) (R(1) = H for aldehydes), where M is the molecular mass of the carbonyl (2,4-dinitrophenyl)hydrazone derivative. The dicarbonyls 2,4-pentanedione and succinic dialdehyde reacted with DNPH to yield predominantly other products. Concentrations measured by ultraviolet spectroscopy (peak area) and by mass spectrometry (abundance of M - 1 ion) were in good agreement. Applications described include the measurement of 34 C(1)-C(18) carbonyls at levels of 0.015-14 parts per billion (ppb) in urban air and the identification of carbonyls at ppb concentrations as reaction products in laboratory studies of the atmospheric oxidation of unsaturated organic compounds.

The Reaction of Unsaturated Aliphatic Oxygenates with Ozone

The reaction of ozone with unsaturated aliphatic oxygenates has been studied at ambient T (287–297 K) and p = 1 atm. of air (RH = 55 ± 10%) with sufficient cyclohexane added to scavenge the hydroxyl radical. Reaction rate constants, in units of 10-18 cm3 molecule-1 s-1, are 10.7 ± 1.4 for methyl trans-3-methoxy acrylate, 63.7 ± 9.9 for 4-hexen-3-one (predominantly the trans isomer), 125 ± 17 for trans-4-methoxy-3-buten-2-one, ≥148 ± 13 for cis-4-heptenal, ≥439 ± 37 for 3- methyl-2-buten-1-ol and ≥585 ± 132 for (cis + trans)-ethyl 1-propenyl ether. The influence of the oxygen-containing substituents on reactivity toward ozone is examined. Unsaturated ethers react with ozone faster than their alkene structural homologues; the reverse is observed for unsaturated esters and unsaturated carbonyls. Major reaction products have been identified by liquid chromatography with ultraviolet detection (LC-UV), particle beam-mass spectrometry (PB- MS) and gas chromatography-mass spectrometry (GC-MS) and are methyl formate and methyl glyoxylate from methyl trans-3-methoxy acrylate, acetaldehyde and 2-oxobutanal from 4-hexen-3-one, propanal and succinic dialdehyde from cis-4-heptenal, hydroxyacetaldehyde and acetone from 3-methyl-2-buten-1-ol, and ethyl formate and acetaldehyde from (cis + trans)-ethyl 1-propenyl ether. PB-MS and GC- MS were also employed to identify new reaction products and to confirm the structure of products tentatively identified in a previous study of the reaction of ozone with five unsaturated oxygenates (Grosjean and Grosjean, 1997a): formic acid and methyl glyoxylate from methyl acrylate, formic acid and formic acetic anhydride from vinyl acetate, 2-oxoethyl acetate and 3-oxopropyl acetate from cis-3-hexenyl acetate, ethyl formate and formic acid from ethyl vinyl ether, and methyl formate from trans-4-methoxy-3- buten-2-one. The nature and formation yields of the reaction products are consistent with (and supportive of) the reaction mechanism: O3 + R1R2C=CR3X → α(R1COR2 + R3C(X)OO) + (1 - α)(R3COX + R1C(R2)OO), where R1, R2 and R3 = H or alkyl, X is the oxygen-containing substituent, R1COR2 and R3COX are the primary products and R1C(R2)OO and R3C(X)OO are the carbonyl oxide biradicals. The variations of the coefficient α, which ranges from 0.25 to 0.61, are discussed in terms of the number and nature of alkyl and oxygen-containing substituents. Subsequent reactions of the alkyl-substituted biradicals R1C(R2)OO and of the biradicals R3C(X)OO that bear the oxygen-containing substituent are discussed. For the biradical CH3CHOO, the ratio ka/kb for the competing pathways of rearrangement to acetic acid (CH3CHOO → CH3C(O)OH, reaction (a) and formation of an unsaturated hydroperoxide (CH3CHOO → CH2=CH(OOH), reaction (b) is 99.9%) and comparable to that for formaldehyde (98.4%) for formic acetic anhydride and for difunctional oxygenated compounds. Uptake in water impingers was lower (19–78%) for monofunctional aldehydes and ketones.

Structure of mucrolidin. Analysis of the influence of some oxygen-containing substituents on the chemical shifts of the protons of the angular methyl of sesquiterpenoids with the eudesmane type of skeleton

A new eudesmanol, mucrolidin has been isolated from the epigeal part of Tanacetopsis mucronata. Its IR, mass, and PMR spectral characteristics have been investigated. Its composition has been established unambiguously by x-ray structural analysis and its spatial structure as 1,4,6-trihydroxy-1α, 5α, 6β, 7α(H)-eudesmane. The interrelationship of the mucrolidin molecules in cyrstal packing is considered. With this sesquiterpenoid as an example, and using the characteristics of the PMR spectra of related compounds, the influence of some oxygen-containing functional groups at C-1, C-4, and C-6 on the chemical shifts of the protons of the methyl at C-10 has been analyzed.

Synthesis of chiral organotin reagents: synthesis of bicyclo[2.2.1]heptan-2-yl(diphenyl)tin hydrides with cis-disposed, oxygen-containing substituents

Alkylation of the methyl 3-triphenylstannylbicyclo[2.2.1]hept-5-ene-2-carboxylate 3 using lithium diethylamide and either methyl iodide or benzyl bromide at –78 °C is stereoselective in favour of the endo-alkylated products 10 and 11. Methylation of the saturated ester 12 is also endo-selective in favour of 13. If the unsaturated ester 3 is deprotonated at 0 °C rather than at –78 °C, the rearranged stannane 17 is obtained as a side-product. The endo-triphenylstannylbicyclo[2.2.1]heptane-2-carboxylate 22 has been prepared from the ester 12 by phenylselenylation, oxidative elimination and reduction using diimide. The triphenylstannanes 13, 17 and 20 have been converted into the alkyl(diphenyl)tin hydrides 27, 28 and 29 and the methoxyalkyltin hydride 36 has also been prepared and characterized. These tin hydrides accelerate the reduction of aryl methyl ketones to 1-arylethanols by phenylsilane, but the reduction product is racemic. Syntheses of the aminobicycloalkyl(triphenyl)stannanes 44, 45 and 48 are described.

Rate constants for the gas-phase reaction of ozone with unsaturated oxygenates

The gas-phase reaction of ozone with a series of unsaturated oxygenates and with 1-pentene has been studied at ambient T (287–296 K) and p=1 atm. of air. Reaction rate constants, in units of 10−18 cm3 molecule−1 s−1, are 0.22±0.05 for 2 (5H)-furanone, 1.08±0.20 for methacrolein, 1.74±0.20 for crotonaldehyde, 5.84±0.39 for methylvinyl ketone, 1.05±0.15 for methyl acrylate, 3.20±0.47 for vinyl acetate, 59.0±8.7 for cis-3-hexenyl acetate, 154±30 for ethylvinyl ether, ≥(315±23) for linalool, and 10.9±1.4 for 1-pentene. The results are compared to literature data for the compounds studied and for other unsaturated oxygenates, and are discussed in terms of reactivity toward ozone as a function of the nature, number, and position of the oxygen-containing substituents (SINGLEBOND)CHO, (SINGLEBOND)C(O)R, (SINGLEBOND)C(O)OR, and (SINGLEBOND)OC(O)R. Atmospheric implications are briefly examined. © 1998 John Wiley & Sons, Inc. Int. J Chem Kinet: 30: 21–29, 1998.

Rate constants for the gas‐phase reaction of ozone with unsaturated oxygenates

The gas-phase reaction of ozone with a series of unsaturated oxygenates and with 1-pentene has been studied at ambient T (287–296 K) and p=1 atm. of air. Reaction rate constants, in units of 10−18 cm3 molecule−1 s−1, are 0.22±0.05 for 2 (5H)-furanone, 1.08±0.20 for methacrolein, 1.74±0.20 for crotonaldehyde, 5.84±0.39 for methylvinyl ketone, 1.05±0.15 for methyl acrylate, 3.20±0.47 for vinyl acetate, 59.0±8.7 for cis-3-hexenyl acetate, 154±30 for ethylvinyl ether, ≥(315±23) for linalool, and 10.9±1.4 for 1-pentene. The results are compared to literature data for the compounds studied and for other unsaturated oxygenates, and are discussed in terms of reactivity toward ozone as a function of the nature, number, and position of the oxygen-containing substituents (SINGLEBOND)CHO, (SINGLEBOND)C(O)R, (SINGLEBOND)C(O)OR, and (SINGLEBOND)OC(O)R. Atmospheric implications are briefly examined. © 1998 John Wiley & Sons, Inc. Int. J Chem Kinet: 30: 21–29, 1998.

Use of incremental models to estimate the retention indexes of aromatic compounds

Pure topologically based incremental models have been developed in order to estimate the retention indexes of aromatic compounds substituted with groups containing the hetero atoms nitrogen, oxygen and halogens. The bond-types of the compounds are counted and used as molecular descriptors. The observed estimation errors are about 1 % for compounds containing no hetero atoms and for those containing halogenated substituents; the errors are approximately 2 % for aromatic compounds with nitrogen- and oxygen-containing substituents. The method is validated by prediction of the retention indexes for an additional group of aromatic compounds (the validation data set).

New variants in the total synthesis of 14?-hydroxy-17?,R-8?,9?-estradiol derivatives

Two procedures were developed for the synthesis of 17α-alkyl-8α,9β-estra-1,3,5(10)-triene-3,14β,17β-triols from 3-methoxy-estra-1,3,5(10),8(9),14(15)-pentaene-17-one (1) using photosensitized oxidation by atmospheric oxygen or ionic hydrogenation in the presence of oxygen. It was shown that 17α-hexynyl-8α,9β-estra-1,3,5(10)-triene-3,14β,17β-triol (23) and its 3-methoxy derivative (26) inhibit K+,Na+-ATPase, with inhibition degree increasing on introduction of an oxygen-containing substituent into position 17. For the first time steroids were found with α2-adrenoblocking action.