Tetrahydrofuran, acidity

Terminal alkyne anions are popular reagents for the acyl anion synthons (RCHjCO"). If this nucleophile is added to aldehydes or ketones, the triple bond remains. This can be con verted to an alkynemercury(II) complex with mercuric salts and is hydrated with water or acids to form ketones (M.M.T. Khan, 1974). The more substituted carbon atom of the al-kynes is converted preferentially into a carbonyl group. Highly substituted a-hydroxyketones are available by this method (J.A. Katzenellenbogen, 1973). Acetylene itself can react with two molecules of an aldehyde or a ketone (V. jager, 1977). Hydration then leads to 1,4-dihydroxy-2-butanones. The 1,4-diols tend to condense to tetrahydrofuran derivatives in the presence of acids. 

The newly formed phosphite triester linkage is unstable to acids and bases and is immediately oxidized to a stable phosphate triester (step 4). A solution of iodine, water, 2,6-dimethylpyridine, and tetrahydrofuran is commonly used. The oxidation is usually complete within 30 seconds. 

The reaction of the o-iodophenol 275 with an alkylallene affords the bcnzo-furan derivative 276[184], Similarly, the reactions of the 6-hydroxyallenes 277 and 279 with iodobenzene afford the tetrahydrofurans 278 and 280. Under a CO atmosphere, CO insertion takes place before the insertion of the allenyl bond, and a benzoyl group, rather than a phenyl group, attacks the allene carbon to give 280. Reaction of iodobenzene with 4,5-hexadienoic acid (281) affords the furanone derivative 282[185]. 

Complete chirality transfer has been observed in the intramolecular allyla-tion of an alcohol with the activated allylic ester of 2,6-dichlorobenzoic acid 338 to give the 2-substituted tetrahydrofuran 339[208]. 

Optically active thiazoline-5-ones (203) can be obtained when cycliza-tion of an optically active N-thiobenzoyl amino acid is brought about by the use of dicyclohexyl carbodiimide in pure chloroform, dich-loromethane (455), or tetrahydrofuran (453. 456) (Scheme 104). 

Potassium hydride Air, chlorine, acetic acid, acrolein, acrylonitrile, maleic anhydride, nitroparaf-flns, A-nitrosomethylurea, tetrahydrofuran, water... 

Therapeutics. Compounds containing the furan or tetrahydrofuran ring are biologically active and are present in a number of pharmaceutical products. Eurfurjdamine [617-89-0] is an intermediate in the diuretic, furosemide. Tetrahydrofurfurylamine [4795-29-3] may also have pharmaceutical applications. 5-(E)imethyiaininomethyi)furfuryi alcohol [15433-79-17 is an intermediate in the preparation of ranitidine, which is used for treating ulcers. 2-Acet5dfuran [1192-62-7] prepared from acetic anhydride and furan is an intermediate in the synthesis of cefuroxime, a penicillin derivative. 2-Euroic acid is prepared by the oxidation of furfural. Both furoic acid [88-14-2] and furoyl chloride [527-69-5] are used as pharmaceutical intermediates. 

With various catalysts, butanediol adds carbon monoxide to form adipic acid. Heating with acidic catalysts dehydrates butanediol to tetrahydrofuran [109-99-9] C HgO (see Euran derivatives). With dehydrogenation catalysts, such as copper chromite, butanediol forms butyrolactone (133). With certain cobalt catalysts both dehydration and dehydrogenation occur, giving 2,3-dihydrofuran (134). 

Heating butanediol or tetrahydrofuran with ammonia or an amine in the presence of an acidic heterogeneous catalyst gives pyrroHdines (135,136). With a dehydrogenation catalyst, one or both of the hydroxyl groups are replaced by amino groups (137). 

Reppe s work also resulted in the high pressure route which was estabUshed by BASF at Ludwigshafen in 1956. In this process, acetylene, carbon monoxide, water, and a nickel catalyst react at about 200°C and 13.9 MPa (2016 psi) to give acryUc acid. Safety problems caused by handling of acetylene are alleviated by the use of tetrahydrofuran as an inert solvent. In this process, the catalyst is a mixture of nickel bromide with a cupric bromide promotor. The hquid reactor effluent is degassed and extracted. The acryUc acid is obtained by distillation of the extract and subsequendy esterified to the desked acryhc ester. The BASF process gives acryhc acid, whereas the Rohm and Haas process provides the esters dkecdy. 

Aqueous mineral acids react with BF to yield the hydrates of BF or the hydroxyfluoroboric acids, fluoroboric acid, or boric acid. Solution in aqueous alkali gives the soluble salts of the hydroxyfluoroboric acids, fluoroboric acids, or boric acid. Boron trifluoride, slightly soluble in many organic solvents including saturated hydrocarbons (qv), halogenated hydrocarbons, and aromatic compounds, easily polymerizes unsaturated compounds such as butylenes (qv), styrene (qv), or vinyl esters, as well as easily cleaved cycHc molecules such as tetrahydrofuran (see Furan derivatives). Other molecules containing electron-donating atoms such as O, S, N, P, etc, eg, alcohols, acids, amines, phosphines, and ethers, may dissolve BF to produce soluble adducts. 

Tetrahydrofuran is polymerized to poly(tetramethylene glycol) with fuming sulfuric acid and potassium biduoride (29). 

Phenyllithium caimot be formed from fluoroben2ene. Instead, the electronegativity of fluorine makes the ortho hydrogen sufficiently acidic to permit reaction with / -butyUithium in tetrahydrofuran at —50°C to give 2-fluorophenyllithium [348-53-8]. An isomer, 4-fluoropheny11ithium [1493-23-8] was reported to be explosive in the soHd state (167). 

Survey of the patent Hterature reveals companies with processes for 1,4-butanediol from maleic anhydride include BASF (94), British Petroleum (95,96), Davy McKee (93,97), Hoechst (98), Huels (99), and Tonen (100,101). Processes for the production of y-butyrolactone have been described for operation in both the gas (102—104) and Hquid (105—108) phases. In the gas phase, direct hydrogenation of maleic anhydride in hydrogen at 245°C and 1.03 MPa gives an 88% yield of y-butyrolactone (104). Du Pont has developed a process for the production of tetrahydrofuran back-integrated to a butane feedstock (109). Slurry reactor catalysts containing palladium and rhenium are used to hydrogenate aqueous maleic acid to tetrahydrofuran (110,111). 

Butane-Based Transport-Bed Process Technology. Du Pont aimounced the commercialization of a moving-bed recycle-based technology for the oxidation of butane to maleic anhydride (109,149). Athough maleic anhydride is produced in the reaction section of the process and could be recovered, it is not a direct product of the process. Maleic anhydride is recovered as aqueous maleic acid for hydrogenation to tetrahydrofuran [109-99-9] (THF). 

An important future use for maleic anhydride is beUeved to be the production of products in the 1,4-butanediol—y-butyrolactone—tetrahydrofuran family. Davy Process Technology has commercialized a process (93) for producing 1,4-butanediol from maleic anhydride. This technology can be used to produce the product mix of the three molecules as needed by the producer. Another significant effort in this area is the tetrahydrofuran plant under constmction in Spain by Du Pont in which butane is oxidized and recovered as maleic acid and the maleic acid is then reduced to tetrahydrofuran (109). 

AlkoxyaLkyl hydroperoxides are more commonly called ether hydroperoxides. They form readily by the autoxidation of most ethers containing a-hydrogens, eg, dioxane, tetrahydrofuran, diethyl ether, diisopropyl ether, di- -butyl ether, and diisoamyl ether (10,44). From certain ethers, eg, diethyl ether (in the following, R = H R = 35 — CH2CH2), the initially formed ether hydroperoxide can yield alcohol on standing, or with acid treatment... 

Instmmental methods of analysis provide information about the specific composition and purity of the amines. QuaUtative information about the identity of the product (functional groups present) and quantitative analysis (amount of various components such as nitrile, amide, acid, and deterruination of unsaturation) can be obtained by infrared analysis. Gas chromatography (gc), with a Hquid phase of either Apiezon grease or Carbowax, and high performance Hquid chromatography (hplc), using siHca columns and solvent systems such as isooctane, methyl tert-huty ether, tetrahydrofuran, and methanol, are used for quantitative analysis of fatty amine mixtures. Nuclear magnetic resonance spectroscopy (nmr), both proton ( H) and carbon-13 ( C), which can be used for quaHtative and quantitative analysis, is an important method used to analyze fatty amines (8,81). 

The /-butyldimethylsilyl group introduced by TBDMIM has a number of advantages in protecting alcohols (6). The sdylated alcohol hydroly2es more slowly than an alcohol sdylated with TMS by a factor of 10 . The sdyl ether is also stable to powerful oxidi2ing and reducing agents, but it can easily be removed by aqueous acetic acid or tetrabutylammonium fluoride in tetrahydrofuran. 

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