Carboxylic Acid Ethyl Ester Research Articles

A Novel Synthetic Routes to New 3-Substituted4-oxo-3,4,5,6,7,8-hexahydropyrido[[4], [4], [5]] thieno[[2], [3]]pyrimidine-7-carboxylic Acid Ethyl Ester Derivatives

Orthoaminoester 1 was investigated by the reaction with ethylchloroformate, 5-phenyl-oxadiazol-2-thione and triethylorthoformate to afford the open structures, 2 , 13 and 15 . These compounds were subjected to ensuing cyclization in one step or more yielding 3-substituted-5,6-dihydro-8H-4-oxopyrido[[4], [4], [5]]thieno[[2], [3]]pyrimidine-7(6H)-carboxylic acid ethyl ester derivatives.

Rhodium‐Catalyzed Reformatsky‐Type Reaction of Ethyl Bromodifluoroacetate.

AbstractFor Abstract see ChemInform Abstract in Full Text.

DESIGN AND SYNTHESIS OF SOME P-SUBSTITUTED STYRYLISOXAZOLE CARBOXYLIC ACID DERIVATIVES AS ANTI-INFLAMMATORY AGENTS

A series of 5-(p-substitutedstyryl)-isoxazole-3-carboxylic acids (4a-g), carboxylic acid ethyl esters (3a-g) and their corresponding amides (6-29) as well as their hydroxamic acid analogues (5a-g) were synthesized and evaluated for their anti-inflammatory activity. The 1,3dicarbonyl systems 2,4-dioxo-6-arylhex-5-enoic acid ethyl esters (2a-g) were the key intermediate for synthesis of the target isoxazole derivatives. The synthesis of these intermediate was achieved through the reaction of chalcones (1a-g), prepared via aldol condensation of the respective substituted benzaldehyde with acetone in alkaline medium, with diethyloxalate. The purity of the synthesized derivatives was determined by thin layer chromatography (TLC) in addition to the microanalyses and their structures were confirmed by different spectroscopic means. The anti-inflammatory activity of twenty-one compounds [(3a,e,f and g); (4a-g); (5a-g); 22; 24 and 25] were assessed, at a dose of 100 mg/kg, by carrageenan-induced paw edema in rats in comparison to indomethacin as a reference drug. The ulcerogenicity of the compounds 3g, 4g and 5g as representatives of the anti-inflammatory active compounds (ester, carboxylic acid and hydroxamic acid) and indomethacin as reference drug was examined under scan electron microscope, after 24 hours of administration of single dose (100 mg/kg) in rats. Significant anti-inflammatory activity was displayed by most of the target derivatives. p-Nitro and p-methoxystyryl isoxazole carboxylic acid derivatives (4e and 4f) revealed 75% inhibition of inflammation after 1 hr reflected the rapid onset of action of these derivatives, which may sustained up to 5 hr as in case of 4e. The anti-inflammatory activity of 5-(p-nitro and pdimethylaminostyryl)-isoxazole-3-carboxylic acid ethyl esters (3e and 3g) being favorably comparable with indomethacin in terms of potency and ulcerogenic liability. The rational behind the synthesis of these compounds and the structure activity relationship are discussed.

Rhodium-catalyzed Reformatsky-type reaction of ethyl bromodifluoroacetate

Treatment of a variety of carbonyl compounds with ethyl bromodifluoroacetate and Et2Zn in the presence of RhCl(PPh3)3 in CH3CN afforded Reformatsky-type products in good to excellent yields in a mild reaction condition. This is a good method to obtain a β-hydroxy-α,α-difluoro carboxylic acid ethyl ester and especially to improve the poor reactivity of ketones.

Temperature and Trinexapac‐Ethyl Effects on Bermudagrass Growth, Dormancy, and Freezing Tolerance

Applications of the plant growth regulator (PGR) trinexapac‐ethyl [4‐(cyclopropyl‐α‐hydroxymethylene)‐3,5‐dioxocyclohexane carboxylic acid ethylester] (TE) can delay winter dormancy in ‘Tifway’ bermudagrass (Cynodon dactylon var. dactylon), which suggests a response to TE when temperatures are suboptimum for bermudagrass growth. The purpose of this study was to investigate the interactive role of temperature and TE in bermudagrass growth responses, dormancy, and freezing tolerance. Trinexapac‐ethyl (0.11 kg a.i. ha−1) was applied in two growth chamber experiments, and across a 2‐yr period in the field. Results indicated that TE reduced vertical shoot growth and increased stolon production, turf density, and quality when applied at high temperatures (35–36°C). While TE effectively reduced vertical shoot growth at low (20–22°C) temperatures, little impact on stolon development was observed under these conditions. Autumn applications of TE when temperatures were cool (≈25°C) at the time of application led to decreased turfgrass density and quality. These responses may explain the effectiveness of using TE to aid in bermudagrass transition to overseeded cool‐season grasses and were probably due to the limited ability of bermudagrass to recover from initial post‐application growth reduction and observed leaf chlorosis. Observed delayed autumn dormancy due to summer applications of TE and accelerated dormancy due to late‐season applications did not conclusively relate to the freezing tolerance of bermudagrass.

Temperature and Trinexapac-Ethyl Effects on Bermudagrass Growth, Dormancy, and Freezing Tolerance

Applications of the plant growth regulator (PGR) trinexapac-ethyl [4-(cyclopropyl-α-hydroxymethylene)-3,5-dioxocyclohexane carboxylic acid ethylester] (TE) can delay winter dormancy in ‘Tifway’ bermudagrass (Cynodon dactylon var. dactylon), which suggests a response to TE when temperatures are suboptimum for bermudagrass growth. The purpose of this study was to investigate the interactive role of temperature and TE in bermudagrass growth responses, dormancy, and freezing tolerance. Trinexapac-ethyl (0.11 kg a.i. ha−1) was applied in two growth chamber experiments, and across a 2-yr period in the field. Results indicated that TE reduced vertical shoot growth and increased stolon production, turf density, and quality when applied at high temperatures (35–36°C). While TE effectively reduced vertical shoot growth at low (20–22°C) temperatures, little impact on stolon development was observed under these conditions. Autumn applications of TE when temperatures were cool (≈25°C) at the time of application led to decreased turfgrass density and quality. These responses may explain the effectiveness of using TE to aid in bermudagrass transition to overseeded cool-season grasses and were probably due to the limited ability of bermudagrass to recover from initial post-application growth reduction and observed leaf chlorosis. Observed delayed autumn dormancy due to summer applications of TE and accelerated dormancy due to late-season applications did not conclusively relate to the freezing tolerance of bermudagrass.

Synthesis of galanthamine

The synthesis of (±)and (-)-galanthamine via 3,4-dihydro-6,7-dimethoxy-4'-oxo-spiro[5H]-2benzazepine-5,1'-[2]cyclohexene]-2(1H)-carboxylic acid ethyl ester (2) is described.

Plant Growth Regulator and Mowing Height Effects on Seasonal Root Growth of Penncross Creeping Bentgrass

Summer decline of creeping bentgrass [Agrostis palustris Huds. (=Agrostis stolonifera var. palustris (Huds.) Farw.] root growth is an annual concern in many regions of the USA. A 2‐yr field study was conducted to investigate the effects of mowing height and plant growth regulator (PGR) treatments on root biomass (RB) patterns in ‘Penncross’ creeping bentgrass, grown on a Wakulla sand (sandy, siliceous, Thermic Psammentic Hapludults) with 94% sand, 4% silt, 2% clay, 24 mg g−1 organic matter, and a pH of 6.1. Plots were maintained at 3.2, 4.0, or 4.8 mm throughout the experiment. Plant growth regulator treatments were trinexapac‐ethyl, [4‐(cyclopropyl‐α‐hydroxymethylene)‐3,5‐dioxo‐cyclohexane carboxylic acid ethyl ester] applied at 0.05 kg a.i. ha−1 and paclobutrazol, {(±)‐(R*,R*)‐β‐[(4‐chloro‐phenyl)methyl]‐α‐(1,1‐dimethylethyl)‐1H‐1,2,4‐triazole‐1‐ethanol} applied at 0.14, 0.28, or 0.56 kg a.i. ha−1 Plant growth regulator treatments initially were applied in April 1997 and were reapplied monthly for 24 mo. Annual variation in air and soil temperature accounted for variable RB across years. Root biomass declined 76% from a May maximum to a minimum in September; however, RB increased between September and January. Turf mowed to a height of 3.2 mm consistently had lower RB than turf maintained at 4.0 or 4.8 mm, and had slower early autumn RB recovery. When averaged across mowing heights, only paclobutrazol (0.56 kg a.i. ha−1) reduced RB and no PGR increased rooting when compared with nontreated turf. From September to January of each year, a PGR by mowing height interaction showed that paclobutrazol applied at 0.56 kg a.i. ha−1 delayed RB recovery in turf mowed to a height of 4.8 mm, while no PGR delayed RB recovery in turf maintained at the 3.2 mm mowing height. Slower RB recovery in turf mowed to 3.2 mm following the September minimum RB was attributed to reductions in turf quality and density, rather than the effects of PGRs. Paclobutrazol only reduced Penncross RB when applied at twice the labeled rate and with greater application frequency than is typical for most PGR use patterns. These results showed that labeled rates of paclobutrazol and trinexapac‐ethyl did not adversely affect root growth under putting green conditions.

Electrochemical fluorination of several methyl and/or ethyl esters of morpholino-substituted carboxylic acids

Seven methyl and/or ethyl esters of carboxylic acids (CH 2CH 2C(O)OEt, CH 2CH 2CH 2C(O)OMe, CH 2CH 2CH 2C(O)OEt, CH(C 2H 5)C(O)OMe, CH( n-C 3H 7)C(O)OMe, CH 2CH 2CH 2CH 2C(O)OEt and CH 2CH 2CH 2CH 2CH 2C(O)OEt) having a morpholino group were subjected to electrochemical fluorination (ECF). On ECF, the corresponding perfluoroacid fluorides bearing a perfluoromorpholino group were obtained in fair to good yields. Yields of the targeted perfluoromorpholino-containing perfluoroacid fluorides were influenced by the α-bond cleavage of the carboxylic acid and also by the kind of alkyl group of the carboxylic acid (the latter offering the possibility of cyclization side reactions). Perfluorooxolanes were formed as a major cyclization by-product from the ECF of morpholino-substituted carboxylic acids when the chain length of the alkyl group of the carboxylic acids had a carbon number of three or more and the structure of the alkyl group was branched in such a way as to allow cyclization. Perfluorodioxolanes were obtained in only small yields as the specific cyclization products when the ethyl esters of carboxylic acids were subjected to ECF. Spectroscopic data, as well as physicochemical properties, are described for the new perfluoroheterocyclic compounds with a perfluoromorpholino group that were produced.

Enantioselective Microbial Reduction with Baker's Yeast on an Industrial Scale

Microbial synthesis is an important contribution to Green Chemistry and production-integrated environmental protection. The example of baker's yeast is used to demonstrate how microorganisms can be versatile reagents for asymmetric synthesis and how microbial technologies can be alternatives and complements to catalytic processes. The commercial viability of enantioselective microbial processes on an industrial scale is shown with the examples of (S)-3-hydroxybutyric acid ethylester (1), (2S,5S)-hexanediol (2) and (1R,2S)-cis-2-hydroxycyclohexane carboxylic acid ethylester (3). The investigation of several competing enzymatic pathways in the living cells during the reduction reaction allows the process to be controlled and makes this technology applicable for the large-scale commercial synthesis of 3.

Plant Growth Regulators and Mowing Height Affect Ball Roll and Quality of Creeping Bentgrass Putting Greens

Questions exist as to whether growth-inhibiting chemicals mimic the effects of reduced mowing heights on putting green ball roll. An experiment was initiated during Spring 1997 to investigate ball roll and visual quality parameters of putting greens maintained at 3.2, 4.0, or 4.8 mm with plant growth regulator (PGR) treatments applied monthly over the course of 1 year. Additional experiments were conducted during Fall 1995 and 1996 and Spring 1996 to investigate diurnal PGR effects on ball roll. All experiments were conducted on pure stands of `Penncross' creeping bentgrass (Agrostis palustris Huds). Treatments included trinexapac-ethyl and paclobutrazol, both inhibitors of gibberellin biosynthesis. In the one-year experiment, mowing height was inversely related to ball roll. However, compromises in turfgrass visual quality and shoot density in `Penncross' turf mowed at 3.2 mm make this a questionable mowing height in areas with severe summer conditions. Ball roll during summer months was reduced by PGRs, suggesting that PGRs have little potential as alternatives to decreasing mowing height for increased ball roll. Paclobutrazol reduced turfgrass quality and shoot density during summer months, suggesting that it be used with caution. Other PGRs, particularly trinexapac-ethyl at 0.05 kg·ha–1 a.i., increased afternoon ball roll by as much as 5% to 10% in diurnal experiments. Use of PGRs on creeping bentgrass putting greens may therefore produce short-lived increases in ball roll with subtle to negative effects on bentgrass growth over more extended periods of time. Chemical names used: 4-(cyclopropyl-α-hydroxymethylene)-3,5-dioxocyclohexane carboxylic acid ethylester (trinexapac-ethyl); (+/–)-(R*,R*)-β-[(4-chloro-phenyl)methyl]-α-(1,1dimethylethyl)-1H-1,2,4-triazole-1-ethanol (paclobutrazol).

Easy Synthetic Approach to p-Aminophenoxy Derivatives Bearing Phosphonic Or Carboxylic Ethyl Ester Groups

Condensation of the ethyl esters of phenyl carboxylic acids or phenyl-phosphonic acids with halonitrobenzenes in anhydrous acetonitrile in presence of potassium carbonate produces 4′-nitrophenoxy-benzoic or benzo-phosphonic acid ethyl esters in good yields. This procedure, which represents a new approach for the nucleophilic condensation, is particularly useful for substrates bearing ancillary reactive groups for which the usual procedure described in literature leads to decomposition products. Reduction of the parent nitro derivatives by hydrazine in the presence of palladium catalyst yields the corresponding amines in very high yield.

Film Structures and Frictional Properties of Monolayers of Partially Fluorinated Carboxylic Acid Ethyl Esters.

Film structure of monolayers of carboxylic acid ethyl esters, having various fluorination ratio at air-water interface, was investigated by measurement of surface pressure-molecular area (π-A) isotherms. The monolayer film structure depends strongly on fluorination ratio of hydrophobic chain. Molecules with a fluorination ratio exceeding 0.55 formed solid-like monolayers, whereas, a liquid-like monolayer was formed. All of the monolayers were transferred onto solid substrate to investigate their surface properties, and to sliding friction test using a ball-on-plate type friction apparatus to investigate frictional properties. It is found that solid monolayers show lower surface free energy, which correlate to lower coefficient of friction. While surface free energy of the monolayers is lower than 30mJ/m2, coefficient of friction of the monolayers is independent on surface free energy. Film energy and two-dimensional modulus of elasticity of the monolayers, developed from the π-A isotherms, were used as parameters to quantitatively characterize the film strength. It is found that coefficient of friction of the monolayers correlated well to film energy and modulus of elasticity: the higher the film energy and modulus of elasticity, the lower the coefficient of friction of the monolayers. The results of research indicate that frictional properties of ultra-thin film are dependent mainly on film strength. Enhancement of mutual intermolecular force, therefore, is a more effective way to improve the lubricating properties of ultra-thin films.

Backbone Stabilized Peptidomimetics Containing Statine-Like Structural Elements: Diastereospecific Synthesis of Trisubstituted Cyclic Ureas and 1,4-Diazepan-2-ones

2-Aminobenzyl substituted 4-amino-3-hydroxy-5-phenyl pentanoic acid (AHPPA) is the central structural element of highly active HIV-protease inhibitors. To obtain conformationally less flexible statine analogs, we stabilized AHPPA via ring formations, e.g. by reaction with 1,1′-carbonyl diimidazole to give six-membered ureas. Reaction of AHPPA with chloroacetyl chloride leads to 1,4-diazepan-2-ones, whereas BOC protected AHPPA is transformed in a two step sequence to 7(S)-benzyl-6-chloro-4-(4-methoxybenzyl)-2-oxo-[1,4]-diazepane-5(S)-carboxylic acid ethylester, likely assisted by transannular influence of N-4. TBDMS protection strategy allows the cyclization of 2-aminobenzyl substituted 4-amino-3-hydroxy-5-phenylpentanal to 7(R)-benzyl-6(S)-hydroxy-5(R)-hydromethyl-4-(4-methoxybenzyl)-(1,4)-diazepan-2-one and 4(R)-benzyl-5(S)-hydroxy-6(R)-hydroxymethyl-1-(4-methoxybenzyl)-tetrahydro-pyrimidino-2-one. In this way, backbone stabilized peptidomimetics containing statine-like structural elements are obtained. 3(R)-(7(R)-Benzyl-6(S)-hydroxy-4-(4-methoxybenzyl)-2-oxo-[1,4]-diazepan-5-yl)-acrylic acid ethylester showed the highest activity against HIV-protease in this series with a Ki value of about 600 nM.

Formation of ethyl esters of long chain carboxylic acids

Ethanol was extracted from the aqueous phase of fermentation into octane in a hollow fibre membrane module and converted using long-chain carboxylic acids into the corresponding esters by immobilized lipase in a reactor integrated into the octane recycle loop. The esters separated from the acids by extraction were recovered and acids and the residue esters re-extracted into octane and recycled.

Investigations on imidazoles 99. Synthesis and some conversions of esters of 4-nitro-5-imidazolylmalonic,-acetoacetic, and-cyanoacetic acids

Some esters of 1-alkyl(1,2-dialkyl)-4-nitro-5-imidazolylmalonic,-acetoacetic, and-cyanoacetic acids have been synthesized by the reaction of 5-chloro(bromo)-1-alkyl(1,2-dialkyl)-4-nitroimidazoles with ethyl esters of carboxylic acids indicated. Some conversions of the compounds obtained have been studied, including ketone and acid decomposition, synthesis of derivatives at the COOH and CO groups, and hydrogenation to 4-aminoimidazole derivatives.

Nature of the Alternate CF2CH2 Chain: Study Based on the Measurement and Comparison of the CAgC's of Aggregators with Alternate Chains and with Hydrocarbon Chains

The saponification rate constants of p-nitrophenyl esters of carboxylic acids with the hydrocarbon chain and the alternate CF2CH2 chain, i.e., H(CH2CH2)(m-1)/2COOC6H4NO2 (C-m) and Cl(CF2CH2)(m-1)/2COOC6H4NO2 (AL-m), in which m stands for the number of chain-carbon atoms and is equal to 3, 5, 7, 9, 11, and 13, have been measured in the 20:80 (v/v) (Φ = 0.20) buffered dioxane−H2O binary solvent. Meanwhile, the fluorescence spectra of 2-(α-naphthyl)ethyl esters of carboxylic acids with the hydrocarbon chain and the alternate CF2CH2 chain, i.e., H(CH2CH2)(m-1)/2COOCH2CH2C10H7 (Fl-C-m) and Cl(CF2CH2)(m-1)/2COOCH2CH2 C10H7 (Fl-AL-m) (m = 3, 5, 7, 9, 11, and 13) have been measured in the Φ = 0.20 dioxane−H2O solvent system. Critical aggregate concentration (CAgC) values derived from the aforesaid kinetic and spectral measurements revealed that the alternate chain possesses a smaller tendency toward aggregation than the hydrocarbon chain does. Therefore, the alternate CF2CH2 chain seems to possess a minute degree of polarity. It has been shown that even neutral organic molecules with a three-carbon chain could show some aggregating tendencies, and our results imply that simple aggregates are formed by a stepwise process.

Lipase-catalyzed preparation of peroxy acids and their use for epoxidation

The lipase-catalyzed reactions of carboxylic acids and carboxylic acid esters with hydrogen peroxide are used to generate various peroxy acids at room temperature and without mineral acids. Whereas Novozym 435 R will only be able to catalyze the conversion of free unbranched carboxylic acids to peroxy acids, α-methylsubstituted carboxylic acid ethylesters can be converted to peroxy acids by perhydrolysis using the same enzyme. These peroxy acids are used in-situ for the epoxidation of unsaturated compounds and thus a new versatile epoxidation method for organic synthesis is proposed.

Polarographic determination of loratadine in pharmaceutical preparations

Loratadine, a potent antihistamine drug, is not directly electroreducible at a dropping mercury electrode; however, by means of a nitration procedure it is possible to obtain a nitro-loratadine derivative which has been identified as 4-(8-chloro-7-nitro-5,6-dihydro-11 H-benzo-[5,6]-cyclohepta-[l,2-b]-pyridin-l l-ylidene)-1-piperidine carboxylic acid ethyl ester. The electrochemical reduction of this derivative at different pHs and concentrations using polarography and cyclic voltammetry was studied. The derivative exhibits a differential pulse polarographic peak due to the reduction of the nitro group. This peak was used in order to develop an analytical procedure for determining loratadine in pharmaceutical dosage forms. The recovery study shows adequate accuracy and precision for the developed assay and the excipients do not interfere in the determination.

Synthesis of N-butyloxycarbonylalanyl-1,4dioxa-7-azaspiro[4,4]nonane-8(S)-carboxylic acid ethyl ester

A four-step method has been developed for the synthesis of N-buryloxycarbonylalanyl-1,4-dioxa-7-azaspiro[4,4]nonane-8(S)-carboxylic acid ethyl ester through the formation of N-benzyloxycarbonyl-1,4-dioxa-7-azaspiro[4,4]nonane-8(S)-carboxylic acid ethyl ester.