Tetrahydrofuran carboxylic acid

Electrochemical fluorination of tetrahydrofuran carboxylic acids derivatives proceeds with preferential formation of F-tetrahydrofurane (5), however, in case of furans containing carbonyl group in the side chain, an interesting formation of spiro-ethers 7 is observed. F-Oxanes 8 and 9 are prepared in low yield by ECF of the corresponding oxane derivatives (Fig. 9.2). 

GHgnard reactions in tetrahydrofuran Carboxylic acids from halides... 

In the discussion of the relative acidity of carboxylic acids in Chapter 1, the thermodynamic acidity, expressed as the acid dissociation constant, was taken as the measure of acidity. It is straightforward to determine dissociation constants of such adds in aqueous solution by measurement of the titration curve with a pH-sensitive electrode (pH meter). Determination of the acidity of carbon acids is more difficult. Because most are very weak acids, very strong bases are required to cause deprotonation. Water and alcohols are far more acidic than most hydrocarbons and are unsuitable solvents for generation of hydrocarbon anions. Any strong base will deprotonate the solvent rather than the hydrocarbon. For synthetic purposes, aprotic solvents such as ether, tetrahydrofuran (THF), and dimethoxyethane (DME) are used, but for equilibrium measurements solvents that promote dissociation of ion pairs and ion clusters are preferred. Weakly acidic solvents such as DMSO and cyclohexylamine are used in the preparation of strongly basic carbanions. The high polarity and cation-solvating ability of DMSO facilitate dissociation... 

Preparation of 7-amino-3-chloro-3-cephem-4-carboxylic acid To a solution of 750 mg (1 55 mmol) of p-nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate hydrochloride in 20 ml of tetrahydrofuran and 40 ml of methanol was added a suspension of 750 mg of prereduced 5% palladium on carbon catalyst in 20 ml of ethanol and the suspension was hydrogenated under 50 psi of hydrogen at room temperature for 45 minutes. The catalyst was filtered and washed with THF and water. The filtrate and catalyst washes were combined and evaporated to dryness. The residue was dissolved in a water-ethyl acetate mixture and the pH adjusted to pH 3. The insoluble product was filtered and triturated with acetone. The product was then dried to yield 115 mg of 7-amlno-3-chloro-3-cephem-4-carboxylic acid. 

Preparation of 2-Cyclopropylcarbony/amido-5-Chlorobenzophenone To 400.5 g (1.73 mols) of 2-amino-5-chlorobenzophenone dissolved in 220 g (2.18 mols) of triethylamine and 3.5 liters of tetrahydrofuran is added cautiously 181 g (1.73 mols) of cyclopropane-carboxylic acid chloride. The reaction is refluxed 2 /2 hours and allowed to cool to room temperature. The solvent is then removed under vacuum to obtain 2-cyclopropylcarbonyl-amido-5-chlorobenzophenone as a residue which is dissolved in 1 liter of methylene chloride, washed twice with 5% hydrochloric acid, and then twice with 10% potassium hydroxide. The methylene chloride solution is then dried over anhydrous magnesium sulfate, filtered and the solvent removed under vacuum. The residue is recrystallized from 1,500 ml of methanol, charcoal-treating the hot solution to give 356 g of 2-cyclopropylcarbonylamido-5-chlorobenzophenone, MP 105° to 105.5°C (69% yield). 

The next major obstacle is the successful deprotection of the fully protected palytoxin carboxylic acid. With 42 protected functional groups and eight different protecting devices, this task is by no means trivial. After much experimentation, the following sequence and conditions proved successful in liberating palytoxin carboxylic acid 32 from its progenitor 31 (see Scheme 10) (a) treatment with excess 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) in ie/t-butanol/methylene chloride/phosphate buffer pH 7.0 (1 8 1) under sonication conditions, followed by peracetylation (for convenience of isolation) (b) exposure to perchloric acid in aqueous tetrahydrofuran for eight days (c) reaction with dilute lithium hydroxide in H20-MeOH-THF (1 2 8) (d) treatment with tetra-n-butylammonium fluoride (TBAF) in tetrahydrofuran first, and then in THF-DMF and (e) exposure to dilute acetic acid in water (1 350) at 22 °C. The overall yield for the deprotection sequence (31 —>32) is ca. 35 %. 

Although lithium aldolates generally display a rather moderate preference for the u/f/z-isomer4, considerable degrees of diastereoselectivity have been observed in the reversible addition of doubly deprotonated carboxylic acids to aldehydes20. For example, the syn- and uw/z-alkox-ides, which form in a ratio of 1.9 1 in the kinctically controlled aldol addition, equilibrate in tetrahydrofuran at 25 C after several hours to a 1 49 mixture in favor of the anti-product20. 

The presence of a large number of chain-ends in the fully synthesized dendrimer molecules makes them highly soluble and also readily miscible, for example with other dendrimer solutions. The solubility is controlled by the nature of the end-groups, so that dendrimers with hydrophilic groups, such as hydroxyl or carboxylic acid, at the ends of the branches are soluble in polar solvents, whereas dendrimers with hydrophobic end-groups are soluble in non-polar solvents. The density of the end-groups at the surface of the dendrimer molecule means that they have proportionately more influence on the solubility than in linear polymers. Hence a dendritic polyester has been shown to be more soluble in tetrahydrofuran than an equivalent linear polyester. 

C 7H,203 5675-70-7) see Bisantrene (R)-(-i)-tetrahydrofuran-2-carboxylic acid (CjHgOj 87392-05-0) see Faropenem sodium ( )-tetrahydrofuran-2-carboxylic acid (CjHgOg 16874-33-2) see Alfuzosin Faropenem sodium tetrahydro-2-furancarboxylic acid anhydride with ethyl hydrogen carbonate (CgHijO, 167391-50-6) see Alfuzosin... 

Fig. 1—2. Hammett diagram for the hydrolysis of imidazolides of aromatic carboxylic acids in water/ tetrahydrofuran (3 1) at 21 °C.[91...

A V -Carbonyldiimidazole (CDI) is prepared in a convenient and safe procedure from phosgene and imidazole as a non-toxic crystalline compound (m.p. 116-118 °C).[5],[6] It reacts almost quantitatively at room temperature or by short and moderate heating with an equimolar quantity of a carboxylic acid in tetrahydrofuran, chloroform, or similar inert solvents within a few minutes to give the corresponding carboxylic acid imidazolide, which is formed under release of carbon dioxide, together with one equivalent of readily separable and recyclable imidazole.Thus, this reaction leads under very mild conditions to the activation of a carboxylic acid appropriate for transacylation onto a nucleophile with an alcohol to an ester, with an amino compound to an amide or peptide, etc. 

With carboxylic acids there was no activation to carboxylic acid imidazolides observed. Reaction with p-toluenesulfonic acid in boiling tetrahydrofuran did not yield the />-toluenesulfonic acid imidazolide, but rather the double p-toluene sulfonate, from which A -sulfonyldiimidazole can be released again quantitatively with imidazole or aniline. Only from the melt of water-free p-toluenesulfonic acid and AyV -sulfonyldiimidazole at 90 °C p-toluenesulfonic imidazolide (m.p. 75.5-77 °C 87% yield) could be obtained1201 (see also Section 10.1.1). 

The reaction of a carboxylic acid with N,Af -carbonyldiimidazolellH33 (abbreviated as CDI), forming an imidazolide as the first step followed by alcoholysis or phenolysis of the imidazolide (second step), constitutes a synthesis of esters that differs from most other methods by virtue of its particularly mild reaction conditions.t41,[5] It may be conducted in two separate steps with isolation of the carboxylic acid imidazolide, but more frequently the synthesis is carried out as a one-pot reaction without isolation of the intermediate. Equimolar amounts of carboxylic acid, alcohol, and CDI are allowed to react in anhydrous tetrahydrofuran, benzene, trichloromethane, dichloromethane, dimethylformamide, or nitromethane to give the ester in high yield. The solvents should be anhydrous because of the moisture sensitivity of CDI (see Chapter 2). Even such unusual solvent as supercritical carbon dioxide at a pressure of 3000 psi and a temperature of 36-68 °C has been used for esterification with azolides.[6]... 

The equilibrium in this first step favors tlie shift to anhydride formation if the second mole of carboxylic acid in the second step with forms imidazole to form a salt that is insoluble in the solvent used (ether, tetrahydrofuran, benzene). 

A selective, mild, and facile reduction of aromatic and aliphatic carboxylic acid imida-zolides to primary alcohols is described in reference [33]. The reaction proceeds in water, water/dioxane or water/tetrahydrofuran solution at room temperature with 2-5 molar equivalents of NaBH4 in about 1 h. 

The group of Lindau has demonstrated the effective O-alkylation of carboxylic acids using a polymer-supported O-methylisourea reagent [123], Under conventional conditions, complete esterifications were observed only after refluxing for several hours in tetrahydrofuran, and the acidic work-up required limited the scope of applicable substituents. In contrast, employing microwave heating led to complete esterifications within 15-20 min, with only 2 equivalents of the polymer-bound... 

The hydrogenation of HMF in the presence of metal catalysts (Raney nickel, supported platinum metals, copper chromite) leads to quantitative amounts of 2,5-bis(hydroxymethyl)furan used in the manufacture of polyurethanes, or 2,5-bis(hydroxymethyl)tetrahydrofuran that can be used in the preparation of polyesters [30]. The oxidation of HMF is used to prepare 5-formylfuran-2-carboxylic acid, and furan-2,5-dicarboxylic acid (a potential substitute of terephthalic acid). Oxidation by air on platinum catalysts leads quantitatively to the diacid. [32], The oxidation of HMF to dialdehyde was achieved at 90 °C with air as oxidizing in the presence of V205/Ti02 catalysts with a selectivity up to 95% at 90% conversion [33]. 

Since Lewis base additives and basic solvents such as tetrahydrofuran are known to deaggregate polymeric organolithium compounds, (21,23,26) it was postulated that ketone formation would be minimized in the presence of sufficient tetrahydrofuran to effect dissociation of the aggregates. In complete accord with these predictions, it was found that the carbonation of poly(styryl)lithium (eq. 9), poly(isoprenyl)-lithium, and poly(styrene-b-isoprenyl)lithium in a 75/25 mixture (by volume) of benzene and tetrahydrofuran occurs quantitatively to produce the carboxylic acid chain ends (8 ). 

Access to the corresponding enantiopure hydroxy esters 133 and 134 of smaller fragments 2 with R =Me employed a highly stereoselective (ds>95%) Evans aldol reaction of allenic aldehydes 113 and rac-114 with boron enolate 124 followed by silylation to arrive at the y-trimethylsilyloxy allene substrates 125 and 126, respectively, for the crucial oxymercuration/methoxycarbonylation process (Scheme 19). Again, this operation provided the desired tetrahydrofurans 127 and 128 with excellent diastereoselectivity (dr=95 5). Chemoselective hydrolytic cleavage of the chiral auxiliary, chemoselective carboxylic acid reduction, and subsequent diastereoselective chelation-controlled enoate reduction (133 dr of crude product=80 20, 134 dr of crude product=84 16) eventually provided the pure stereoisomers 133 and 134 after preparative HPLC. 

One fact to keep in mind with such phases is that weak acid cation-exchange materials based on carboxylic acid functional groups are subject to esterification in the presence of alcohol containing eluents. Even thongh typical eluent conditions (i.e., weakly acidic aqneous eluents containing alcohol) do not favor ester formation, such stationary phases typically exhibit slowly declining capacity when operated in the presence of alcohol-containing eluents. Consequently, such columns are normally operated with acetonitrile, tetrahydrofuran or acetone rather than with methanol, in order to avoid this problem. 

Hydrindene, see Indan Hydrindonaphthene, see Indan 1,8-Hydroacenaphthylene, see Acenaphthene Hydrobroinic ether, see Ethyl bromide Hydrocarbon propellant A-17, see Bntane Hydrochloric ether, see Chloroethane Hydrofuran, see Tetrahydrofuran Hydrogen carboxylic acid, see Formic acid Hydrophenol, see Cyclohexanol Hydroqninol, see Hydroquinone Hydroqninole, see Hydroquinone a-Hydroqninone, see Hydroquinone p-Hydroqninone, see Hydroquinone 6-Hydroxyacenaphthenone, see Acenaphthene Hydroxybenzene, see Phenol... 

SYNTHESIS and CHARACTERIZATION of O-ALKYLATED EXTRACTS. Alkylation occurs when tetrabutylanunonium hydroxide is used to promote the reaction of the alkyl iodide with the coal in tetrahydrofuran.(14) The alkylation reaction occurs primarily on acidic oxygen functionalities such as phenolic hydroxyl and carboxylic acid groups, as shown below. 

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