Intermediate Alcohol Research Articles

A facile synthesis of fused aromatic spiroacetals based on the 3,4,3′,4′-tetrahydro-2,2′-spirobis(2H-1-benzopyran) skeleton

Abstract The facile synthesis of a series of aromatic 6,6-spiroacetals based on the parent 3,4,3′,4′-tetrahydro-2,2′-spirobis(2H-1-benzopyran) heterocyclic system is reported. Key steps included the use of a Sonogashira coupling for the synthesis of an aryl acetylene that was coupled to an aryl aldehyde to form a propargyl alcohol intermediate. Hydrogenation of the alkynol followed by oxidation produced a masked dihydroxy ketone that upon treatment with trimethylsilyl bromide underwent deprotection and cyclisation to the fused aromatic spiroacetal.

Stereoselective Enzymatic Synthesis of Chiral Alcohols with the Use of a Carbonyl Reductase from Candida magnoliae with Anti-Prelog Enantioselectivity

In our effort to search for carbonyl reductases with anti-Prelog enantioselectivity, the activity and enantioselectivity of a carbonyl reductase from Candida magnoliae have been examined with various ketones of diverse structures. This carbonyl reductase catalyzed the reduction of a series of ketones, alpha- and beta-ketoesters, to anti-Prelog configurated alcohols in excellent optical purity. The usefulness of this carbonyl reductase has been demonstrated by synthesis of several chiral alcohol intermediates of pharmaceutical importance.

Uptake, metabolism, and toxicity of methyl tert-butyl ether (MTBE) in weeping willows

Methyl tert-butyl ether (MTBE) is a high volume production chemical and the most commonly used gasoline oxygenate. Uptake, metabolism and toxicity of MTBE in trees were investigated in this study. Pre-rooted weeping willows ( Salix babylonica L.) were exposed to hydroponic solution spiked with MTBE and incubated at 25.0 ± 1 °C for 168 h. The normalized relative transpiration (NRT) rate of weeping willows was used to determine toxicity. MTBE and possible intermediate tert-butyl alcohol (TBA) in solution, tissues of aerial parts of plants, and air were analyzed. Results from the toxicity test showed that severe signs of toxicity (the reduction of the NRT ≥35%) were only found at the treatment group with high doses of MTBE 400 mg L −1. Neither chlorosis of leaves nor large reduction in the NRT was observed at MTBE exposure to weeping willows ≤200 mg L −1. Almost all applied MTBE was removed from the hydroponic solution by plants in all treatment groups. Small amounts of MTBE were detected in the plant tissues, but a large fraction of the applied MTBE was found in the air through plant transpiration. Mass balance studies showed that MTBE was assimilated into the plants from hydroponic solution but was not metabolized during transport in the plant. Phytovolatilization was the only relevant removal process for MTBE. Transpiration stream concentration factor (TSCF), an important parameter for design of engineered MTBE phytoremediation systems, was estimated to be 1.12. In conclusion, although this compound is persistent to the attack by plant enzymes, atmospheric MTBE is much more susceptible to photo-oxidation for decomposition. Phytoremediation of MTBE polluted soils and groundwater is an alternative to presently available remediation technologies.

Lipases: Useful biocatalysts for the preparation of pharmaceuticals

Biocatalysis offers a clean and ecological way to perform chemical processes, in mild reaction conditions and with high degree of selectivity. The use of enzymes, specially lipases, in organic solvents proves an excellent methodology for the preparation of single-isomer chiral drugs. This review covers some general aspects and representative examples of the use of lipases for the enantioselective or regioselective preparation of alcohol and amine intermediates in the synthesis of pharmaceuticals.

Selective Oxidation of Alkanes with Molecular Oxygen and Acetaldehyde in Compressed (Supercritical) Carbon Dioxide as Reaction Medium

The oxidation of cycloalkanes or alkylarenes with molecular oxygen and acetaldehyde as sacrificial co-reductant occurs efficiently in compressed (supercritical) carbon dioxide (scCO2) under mild multiphase conditions. No catalyst is required and high-pressure ATR-FTIR online measurements show that a radical reaction pathway is heterogeneously initiated by the stainless steel of the reactor walls. For secondary carbon atoms, high ketone to alcohol ratios are observed (3.5-7.9), most probably due to fast consecutive oxidation of alcoholic intermediates. Since C--C scission reactions are detected only to a very small extent, tertiary carbon atoms are transformed into the corresponding alcohols with high selectivity. Detailed analysis of the product distributions and other mechanistic evidence suggest that acetaldehyde acts not only as the sacrificial oxygen acceptor, but also as an efficient H-atom donor for peroxo and oxo radicals and as a crucial reductant for hydroperoxo intermediates. In comparison to other inert gases such as compressed N2 or Ar, the use of carbon dioxide was shown to increase the yields of alkane oxygenates under identical reaction conditions.

Synthesis of l- and d-β-3‘-Deoxy-3‘,3‘-difluoronucleosides

Both L- and D-beta-3'-deoxy-3',3'-difluoronucleosides were synthesized starting from the key intermediate difluorohomoallyl alcohol 11. Deoxo-Fluor was accidentally found to be efficient in reversing the hydroxyl configuration of 34, and the desired product 41 was provided in good yield.

Synthesis and Odor Properties of Substituted Indane‐2‐carboxaldehydes. Discovery of a New Floral (Muguet) Fragrance Alcohol

AbstractEight substituted indane‐2‐carboxaldehydes (= 2,3‐dihydro‐1H‐indene‐2‐carboxaldehydes), related to conformationally constrained analogues of floral‐type odorants, were synthesized in order to examine the effect of modifying the lipophilic part of the odorants (Schemes 1 and 2). None of the modified compounds showed better olfactive properties than the original ones (Tables 1 and 2), but an intermediate alcohol, 29, revealed itself as a valuable new member in the family of floral muguet (lily‐of‐the‐valley)‐type odorants.

Acetone condensation and selective hydrogenation to MIBK on Pd and Pt hydrotalcite-derived Mg [sbnd]Al mixed oxide catalysts

The condensation and selective hydrogenation of acetone to methyl isobutyl ketone (MIBK) was studied on a directly comparable series of 0.1–1.5 wt% Pd and Pt catalysts supported on hydrotalcite (HT)-derived Mg Al mixed-oxides in a liquid-phase batch micro-reactor at 99–153 °C and 400 psig. The support catalyzes the condensation of acetone to diacetone alcohol (DAA) and its subsequent dehydration to mesityl oxide (MO); Pd and Pt catalyze the selective hydrogenation of MO to MIBK. The net yield of MIBK is independent of metal type and loading, depending only on the wt% of exposed metal. However, the by-products are quite different-Pt/HT is more selective for the direct hydrogenation to isopropanol (IPA) while Pd/HT forms more of the intermediate diacetone alcohol (DAA). Among the Pd- and Pt-based catalysts examined, the 0.1 wt% Pd/HT gives the maximum MIBK yield of ∼32%, with an unusually low selectivity to IPA, 0.6 mol% compared to 15 mol% for the next best catalyst. This appears to be due to its higher basicity, and (to a lesser extent) to its minimal concentration of metal sites. This metal loading is sufficient to fully hydrogenate mesityl oxide to MIBK, and it also shows minimal acetone hydrogenation to isopropanol. A study of physically mixed Pd/silica + HT versus Pd/HT shows that the acid/base and hydrogenation functions need not be molecularly close.

Regioselective Synthesis of 2,6-Dimethyltetralin: Key Precursor to 2,6-Dimethylnaphthalene

A novel regioselective synthesis for 2,6-dimethyltetralin (2,6-DMT), a key precursor to 2,6-dimethylnaphthalene (2,6-DMN), is described. The synthesis comprises the following three steps; the Heck reaction between commercially available 4-bromotoluene and 3-methyl-3-buten-1-ol, the catalytic reduction of the coupling products, and the acid-catalyzed cyclization of the alcohol intermediate. The process has an advantage over the established processes in that 2,6-DMT is obtained as the only isomer, and the isomerization and/or the complicated separation and purification steps are not required to produce pure 2,6-DMT. 2,6-DMN could be also obtained as a major product depending on the cyclization conditions.

Three‐Component Reaction of Aryl Diazoacetates, Alcohols, and Aldehydes (or Imines): Evidence of Alcoholic Oxonium Ylide Intermediates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Hydrodeoxygenation of methyl esters on sulphided NiMo/γ-Al 2O 3 and CoMo/γ-Al 2O 3 catalysts

Wood-derived bio-oil contains high amounts of compounds with different oxygen-containing functional groups that must be removed to improve the fuel characteristics. Elimination of oxygen from carboxylic groups was studied with model compounds, methyl heptanoate and methyl hexanoate, on sulphided NiMo/γ-Al 2O 3 and CoMo/γ-Al 2O 3 catalysts in a flow reactor. Catalyst performances and reaction schemes were addressed. Aliphatic methyl esters produced hydrocarbons via three main paths: The first path gave alcohols followed by dehydration to hydrocarbons. Deesterification yielded an alcohol and a carboxylic acid in the second path. Carboxylic acid was further converted to hydrocarbons either directly or with an alcohol intermediate. Decarboxylation of the esters led to hydrocarbons in the third path. No oxygen-containing compounds were detected at complete conversions. However, the product distributions changed with time, even at complete conversions, indicating that both catalysts deactivated under the studied conditions.

A family of high-buffering capacity diamino sulfate isoelectric buffers for pH-biased isoelectric trapping separations

pH-biased isoelectric trapping separations are hindered by the lack of suitable isoelectric buffers with pI values in the 5.8 < pI range. Two generic approaches are described here for the cost-effective synthesis of a family of diamino sulfate buffers that have high buffering capacities in their isoelectric state: the first approach relies on the sulfation of existing, commercially available diamino alcohol intermediates, the second approach calls for the synthesis of diamino alcohols from epichlorohydrin and widely available secondary amines, and subsequent sulfation of the new diamino alcohol. The diamino sulfate buffers are recovered in isoelectric state, in high purity. Four members of the family having pI values in the 5.8 < pI < 8.9 range have been synthesized, analytically characterized by capillary electrophoresis (CE), electrospray ionization-time of flight-mass spectrometry (ESI-TOF-MS), 1-D and 2-D nuclear magnetic resonance (NMR) spectroscopy, and X-ray crystallography. All four diamino sulfates have been successfully used as pH biasers in the receiving stream in preparative-scale pH-biased isoelectric trapping protein separations.

Three-Component Reaction of Aryl Diazoacetates, Alcohols, and Aldehydes (or Imines): Evidence of Alcoholic Oxonium Ylide Intermediates

The Rh(II)-catalyzed three-component reaction of aryl diazoacetates, alcohols and aldehydes was explored, which provided evidence of alcoholic oxonium ylide formation for O-H insertion. A new C-C bond formation reaction where alcoholic oxonium ylides were trapped by electron-deficient aryl aldehydes (or imines) was realized.

The Role of Aromatic Radical Cations and Benzylic Cations in the 2,4,6-Triphenylpyrylium Tetrafluoroborate Photosensitized Oxidation of Ring-Methoxylated Benzyl Alcohols in CH2Cl2 Solution

A steady-state and laser flash photolysis (LFP) study of the TPPBF(4)-photosensitized oxidation of ring-methoxylated benzyl alcohols has been carried out. Direct evidence on the involvement of intermediate benzyl alcohol radical cations and benzylic cations in these reactions has been provided through LFP experiments. The reactions lead to the formation of products (benzaldehydes, dibenzyl ethers, and diphenylmethanes) whose amounts and distributions are influenced by the number and relative position of the methoxy substituents. This behavior has been rationalized in terms of the interplay between the stabilities of benzyl alcohol radical cations and benzyl cations involved in these processes. A general mechanism for the TPPBF(4)-photosensitized reactions of ring-methoxylated benzyl alcohols has been proposed, where the alpha-OH group of the parent substrate acts as the deprotonating base promoting alpha-C-H deprotonation of the benzyl alcohol radical cation (formed after electron transfer from the benzyl alcohol to TPP) to give a benzyl radical and a protonated benzyl alcohol, precursor of the benzylic cation. This hypothesis is in contrast with previous studies, where formation of the benzyl cation was suggested to occur from the neutral benzyl alcohol through the Lewis acid action of excited TPP(+) (TPP).

New Mechanism for the Catalytic Oxidation of Lignin to Vanillin

The previously proposed mechanism for lignin oxidation to vanillin was supported experimentally. This process begins with the formation of a phenoxyl radical and ends with the step of retroaldol cleavage of substituted coniferaldehyde to vanillin. The oxidation of model compounds was studied, and experimental evidence for the proposed mechanism was obtained. The postulated intermediate coniferyl alcohol was detected in the oxidation of eugenol. The proposed mechanism was supported by kinetic data and the composition of the oxidation products of vanillideneacetone, lignosulfonates, eugenol, isoeugenol, guaiacylethanol, and guaiacylpropanol.

Enantioselective synthesis of a hindered furyl substituted allyl alcohol intermediate: a case study in asymmetric synthesis

In the course of the synthesis of the DEFG ring system of cneorin C 1, we were faced with the task of preparing the furyl substituted allyl alcohol 5 enantioselectively. Several different methods starting from enantioselective zinc-mediated alkylations were attempted, but none of them proved entirely satisfactory. The solution turned out to be enzymatic kinetic resolution through a highly enantioselective ( E>300) acylation in the presence of Candida antarctica lipase A.

Tris(trimethylsilylmethyl)alane: an aldehyde selective peterson methylenation reagent

Tris(trimethylsilylmethyl)alane (TTMA) is a rapid, efficient, and highly aldehyde-selective trimethylsilylmethylating reagent. A solid lithium halide complex of the reagent, TTMA · 3LiBr (TTMAs), is particularly effective in this transformation to the Peterson alcohol intermediate.

Carbon-carbon bond cleavage by cytochrome p450(BioI)(CYP107H1).

Cytochrome p450(BioI)(CYP107H1) is believed to supply pimelic acid equivalents for biotin biosynthesis in Bacillus subtilis: we report here that the mechanistic pathway adopted by this multifunctional p450 for the in-chain cleavage of fatty acids is via consecutive formation of alcohol and threo-diol intermediates, with the likely absolute configuration of the intermediates also reported.

Regioselective Cleavage of Trisubstituted Epoxy-Linkage Using Lithium Trialkylborohydride Reagents: A New Route to the Key Intermediate of Maxacalcitol

Optimal conditions for the reductive cleavage of a trisubstituted epoxide leading regioselectively to the key intermediate tertiary alcohol of Maxacalcitol, used for the treatment of secondary hyperparathyroidism and psoriasis, have been established using lithium tri(sec-butyl)borohydride (L-Selectride) in THF.

Higher-alcohols biorefinery: improvement of catalyst for ethanol conversion.

The concept of a biorefinery for higher-alcohol production is to integrate ethanol and methanol formation via fermentation and biomass gasification, respectively, with conversion of these simple alcohol intermediates into higher alcohols via the Guerbet reaction. 1-Butanol results from the self-condensation of ethanol in this multistep reaction occurring on a single catalytic bed. Combining methanol with ethanol gives a mixture of propanol, isobutanol, and 2-methyl-1-butanol. All of these higher alcohols are useful as solvents, chemical intermediates, and fuel additives and, consequently, have higher market values than the simple alcohol intermediates. Several new catalysts for the condensation of ethanol and alcohol mixtures to higher alcohols were designed and tested under a variety of conditions. Reactions of methanol-ethanol mixtures gave as high as 100% conversion of the ethanol to form high yields of isobutanol with smaller amounts of 1-propanol, the amounts in the mixture depending on the starting mixture. The most successful catalysts are multifunctional with basic and hydrogen transfer components.