Tetrahydrofuran, as reaction solvent

Methylmagnesium chloride has been added to various d-(4-substituted-phenyl) <5-oxo esters 15 (X = H, Cl 13, F, Cl, Br, OC11,) which provides the diastereomeric -lactones 1642. The electronic properties of the phenyl 4-substituent have no significant influence on the diastereoselectivity. Except for the 4-methoxyphenyl compound, which is unreactive even at 60 °C, a ratio of ca. 40 60 in favor of the anti-Cram product is observed at 60 "C in tetrahydrofuran as reaction solvent. Lowering the reaction temperature to 0 °C slightly increases the anti-Cram selectivity in the case of the 4-fluoro-, 4-chloro-, and 4-bromo-substituted compounds. On the other hand, a complete loss of reactivity is observed with the <5-phenyl- and <5-(4-methylphenyl)-substituted h-oxo esters. 

In addition to the boron trifluoride-diethyl ether complex, chlorotrimcthylsilanc also shows a rate accelerating effect on cuprate addition reactions this effect emerges only if tetrahydrofuran is used as the reaction solvent. No significant difference in rate and diastereoselectivity is observed in diethyl ether as reaction solvent when addition of the cuprate, prepared from butyllithium and copper(I) bromide-dimethylsulfide complex, is performed in the presence or absence of chlorotrimethylsilane17. If, however, the reaction is performed in tetrahydrofuran, the reaction rate is accelerated in the presence of chlorotrimethylsilane and the diastereofacial selectivity increases to a ratio of 88 12 17. In contrast to the reaction in diethyl ether, the O-silylated product is predominantly formed in tetrahydrofuran. The alcohol product is only formed to a low extent and showed a diastereomeric ratio of 55 45, which is similar to the result obtained in the absence of chlorotrimethylsilane. This discrepancy indicates that the selective pathway leading to the O-silylated product is totally different and several times faster than the unselective pathway" which leads to the unsilylated alcohol adduct. A slight further increase in the Cram selectivity was achieved when 18-crown-6 was used in order to increase the steric bulk of the reagent. 

Addition of alkynes to a-alkoxy aldehydes is most favorably performed with the corresponding zinc reagents (Table 12)46. As with Grignard reagents, the chelation-controlled addition of zinc alkynes proceeds with higher diastereoselectivity when diethyl ether rather than tetrahydrofuran is used as reaction solvent. 

The nucleophilic addition of Grignard reagents to a-epoxy ketones 44 proceeds with remarkably high diastereoselectivity70. The chelation-controlled reaction products are obtained in ratios >99 1 when tetrahydrofuran or tetrahydrofuran/hexamethylphosphoric triamide is used as reaction solvent. The increased diastereoselectivity in the presence of hexamethylphos-phoric triamide is unusual as it is known from addition reactions to a-alkoxy aldehydes that co-solvents with chelating ability compete with the substrate for the nucleophile counterion, thus reducing the proportion of the chelation-controlled reaction product (vide infra). 

With respect to the nucleophilic addition of organocopper reagents, a sharp contrast between the rigid isopropylidene glyceraldehyde and its open-chained analog, 2,3-bis(benzyloxy)propanal. was observed (compare Tables 15 and 16). With the isopropylidene-protected aldehyde a high syn diastereoselectivity could only be obtained when tetrahydrofuran was used as reaction solvent, and the diastereoselectivity dropped considerably in diethyl ether. In contrast, the latter solvent allows excellent syn selectivities in additions to the dibenzyl-protected glyceraldehyde81. On the other hand, tetrahydrofuran yields better results than diethyl ether in the... 

In several separate small scale experiments, It was noted that the coupling reaction was not impeded by adding pyridine, triethylamine, t-butyl alcohol, chlorotrimethylsilane, or diisopropylamine to the reaction mixture before adding the nickel catalyst. These results suggest that a variety of functional groups can be present in the enone partner of the coupling reaction. In addition toluene can be used instead of tetrahydrofuran as the solvent. 

An azo coupling could be prevented by changing tetrahydrofurane as a solvent to dimethylsulfoxide or by adding 18-crown-6 ether to the THF-reaction mixture. The splitting of the coordination complex follows Scheme 3-49. 

Thus, 3-acclyl-4-hydroxychromcn-2-one (17) reacts with bromine in a conventional manner (bromine/acetic acid) to give substitution products at the aromatic nucleus as the major product [47,48]. For example, 3-acetyltropolone and 4-acetyltropolone were reacted with bromine to afford the corresponding substitution products at the tropolone nucleus as the main products [49,50]. For this reason, 17 was treated with phenyltrimethylammo-nium tribromide [51-53] (Scheme 6). The reaction was carried out at room temperature using tetrahydrofuran as the solvent. The structure of 18 was determined on the basis of spectral data and elemental analysis. 

Interesting publications of work undertaken in this field of reactivity by a research group in (what at that time was part of) the USSR, unfortunately, was published mainly in rather inaccessible journals. The rates of reaction of phenylacetylene with ethyl- and phenylmagnesium bromide were measured in diethyl ether and in tetrahydrofuran, respectively [32]. The results, presented in Table 8, clearly show the dramatic change in the second-order rate constants, when diethyl ether is replaced by tetrahydrofuran as the solvent. The same effect had been found in 1968 by others [33] for the reaction of benzylmagnesium chloride with phenylacetylene at 0°C the second-order rate constant (/c2 X 10 L mol sec ) was 0.008 in diethyl ether and 84 in tetrahydrofuran, a change by a factor of (more than) 10 thousand. 

A similar rate expression was first obtained by Natta et al. [19]. The problem with this system, however, is that the yield after 4 h reaction time is only 14 % at 110 °C with Ph, = Pco = 40 MPa and tetrahydrofuran as the solvent[20j. In order to obtain a higher yield, Hidai et al. [20] added a certain amount of Ru3(CO) 2 to the cobalt carbonyl-containing reaction system. Although the hydro-formylation activity of this carbonyl compound is relatively low (cf. Section 2.1.1.2.1), about one-third of that with the cobalt complex, the authors observed a marked increase of the initial reaction rate with increasing ruthenium content. They suggested that the ruthenium species opens an additional route for forming the final C-H bond. Thus, it is to be expected that there is a second reaction rate, 1-2, which can be given by eq. (5) ... 

Currently, the best route to phenyllithium-tricarbonylchromium is one in which the reaction between benzene-tricarbonylchromium and BuLi is conducted in 1 1 ethyl ether-tetrahydrofuran as the solvent system at —40°C for one hour. Under these conditions, carbonation gives benzoic acid-tricarbonylchromium in 61% yield, and the intermediate organolithium reagent has been used to form other functionally substituted derivatives of benzene-tricarbonylchromium in good yield (41, 42). 

At —60° in ether, high yields of phosphonites were obtained provided the reaction mixture was distilled directly and not hydrolyzed (102). Dilute aqueous acid readily hydrolyzes phosphonites—a fact which could reduce the efficiency of the Grignard synthesis (53). Experiments by others have supported these suspicions (100,104,176). Probably of equal importance is the use of tetrahydrofuran as a solvent which appears to improve the yields in the cases cited. Improved solvation of the Grignard reagent and the organophosphorus products may be influential. Double displacement of OR occurs at 40° with dibutyl vinylphosphonite which demonstrates the importance of the temperature parameter (99). Even the reactive phosphinite (17) survives at... 

The reaction between acetylene and carbon monoxide takes place at 180-200 C (355-390°F) and 40-55 bars (590-800 psig). The chemistry, which employs a NiBr2/CuI catalyst in tetrahydrofuran as the solvent, is illustrated in Eq. (30) ... 

A researcher prepared a Grignard reagent using tetrahydrofuran as the solvent. Magnesium turnings were added to the solvent followed by iodine to initiate the reaction. A bromobenzene derivative was added to the reaction mixture incrementally, and the reaction was left unattended in a chemical hood. After about 20-30% of the bromobenzene derivative had been added, a sudden exothermic reaction caused the solvent to boil, blowing most of the reaction mixture out of the flask. 

Under special reaction conditions (crotyl chloride, tetrahydrofuran as the solvent) however the yield of the desired product can nevertheless be as high as 90%. 

Organolithium compounds and Grignard reagents are prepared by reaction of the metal with an alkyl, aryl, or vinylic halide, usually in diethyl ether or tetrahydrofuran as the solvent. 

The combination of iodine/imidazole reagent in tetrahydrofuran as a solvent produced glycosylamines in quantitative yields. It is worth mentioning that iV-benzylglucosylamine was produced even faster under this reaction condition than when using the Martin protocol. ... 

Excess alkylating reagent is required if the tetraorganotin is desired as the exclusive product. In commercial practice, the stoichiometry is kept at or below 4 1, since the cmde product is usually redistributed to lower organotin chlorides in a subsequent step and an ether is used as the solvent (86). The use of diethyl ether in the Grignard reaction has been generally replaced with tetrahydrofuran. 

Uses. Approximately 70% of the U.S. production is used to make poly(tetramethylene ether glycol) [25190-06-1] (PTMEG), also known as poly-THE, which is used in the production of urethane elastomers, polyurethane fibers (ether-based spandex), and copolyester—ether elastomers. PTMEG is also the fastest growing use (see PoLYETPiERS, TETRAHYDROFURAn). The remaining production is used as a solvent for the manufacture of poly(vinyl chloride) cements and coating, precision magnetic tape, a reaction solvent in the production of pharmaceuticals, and other miscellaneous uses. 

---