Tetrahydrofuran methanol elimination

MonofluoToalkanes and vicinal difluoroalkanes are dehydrofluonnated if strong enough bases are applied [10 12] In 5-fluorononane and fluorocyclodo-decane, elimination by means of sodium methoxide in methanol gives cis- and trans allcenes in respective yields of 8 and 21% and in ratios of 1 2 2 2 4, however, the bulky lithium diisopropyl amide m tetrahydrofuran produces trdns-isomers almost exclusively The strength of the base does not have much effect on the rate of elimination, but the lithium cation causes considerable acceleration [10] (equation 10)... 

Difluorododecane is unaffected by sodium methoxide in methanol, but its treatment with potassium tert-butoxide in tetrahydrofuran eliminates hydrogen fluonde stereospecifically rneso and dl compounds give, respectively, ( )- and (2) 6 fluoro 6 dodecene [12] (equation 11)... 

The elimination of sulfur dioxide from thiirane dioxides leading to the corresponding alkenes is not the only result of base-induced reactions other products are also formed. This fact raises the question of the mechanistic pathway of this reaction. In general, the thiirane dioxide is treated with a large excess of the base in an appropriate solvent for several hours at room temperature or below. Bases commonly used are 2n NaOH (in water), NaOCH3 (in methanol), t-BuO-K + (in f-BuOH) and BuLi (in tetrahydrofuran) or KOH-CCU (in t-BuOH)16-19"112 113. 

Unlike 1,3-dithiepin anion 144a, the evidence for the instability of 145a and for the lack of aromaticity associated with lOn-electron delocalization through the sulfur atom has been reported 91,92). The reaction of the disodium salt of c/s-dimercaptoethylene (155) with either l,2-dibromo-3-propanol or l,3-dibromo-2-propanol yielded 6,7-dihydro-5f/-l,4-dithiepin-6-ol (156). Treatment of the methoxy derivative 157 derived from 156 with two equivalents of lithium dicyclohexylamide resulted in an effective elimination of methanol to give 5//-l,4-dithiepin (145) as a colorless liquid. Lithiation of 145 with n-butyllithium in tetrahydrofuran at —70 °C... 

Adenosine analogues where the furanose ring was replaced with alternative dihydro- and tetrahydrofurans were prepared from 6-chloro-9-(4-methylenetetrahydrofuran-3-yl)-9/7-purine <2002T4865>. Of particular interest was the transformation of the exocyclic alkene on the THF ring first by dihydroxylation, then elimination to yield (4-(6-aminopurin-9-yl)-2,5-dihydrofuran-3-yl)methanol after amination of the purine ring at C-6. This A-alkenylpurine was reduced (Pd/C, H2, 25 psi, 73% yield) to provide the tetrahydrofuran-3-yl derivative. 

Different synthetic routes have been used to prepare these carbenes (Scheme 8.6). The most common procedure is the deprotonation of the conjugate acid. In early experiments, sodium or potassium hydride, in the presence of catalytic amounts of either f-BuOK or the DMSO anion were used. ° Then, Herrmann et al. showed that the deprotonation occurs much more quickly in liquid ammonia as solvent (homogeneous phase), and many carbenes of type IV have been prepared following this procedure. In 1993, Kuhn and Kratz" developed a new and versatile approach to the alkyl-substituted N-heterocyclic carbenes IV. This original synthetic strategy relied on the reduction of imidazol-2(3//)-thiones with potassium in boiling tetrahydrofuran (THF). Lastly, Enders et al." reported in 1995 that the 1,2,4-triazol-5-ylidene (Vila) could be obtained in quantitative yield from the corresponding 5-methoxy-l,3,4-triphenyl-4,5-dihydro-l//-l,2,4-triazole by thermal elimination (80 °C) of methanol in vacuo (0.1 mbar). 

Studies have also been carried out in systems containing excess BF3 (17,18). The results (18) show that when the base is dimethyl ether, anisole, tetrahydrofuran, or pyridine, the exchange of BF3 is rapid and probably proceeds through an electrophilic displacement reaction in which the excess BF3 attacks the complex. These reactions all have activation energies of less than 10 kcal/mole, eliminating the possibility of a dissociation process. The data available, however, do not allow a complete evaluation of the reaction mechanism. Studies carried out on BF3-methanol complexes by 19F NMR (17) indicate displacement reactions having an activation energy of 5.3 kcal/mole. 

Cyclization to the benzo[c]phenanthridine (127) competes with rearrangement to the ring-expanded product (128) on irradiation of the amine oxide (129). A practical synthesis of the chlorin macrocycle (130) has been developed by irradiation of the seco-compound (131) in tetrahydrofuran containing TFA and Hiinig s base this is thought to take place by photocyc-lization of the ISrr-tautomer (132), followed by elimination of methanol. Analogous approaches have been employed in the syntheses of ( )-bonellin dimethyl ester and 20-methyl- and 20-cyano-isobacteriochlorins. " ... 

The recovery of the waste streams was complex, since a series of azeotropes had to be separated. Different alternatives were simulated and initial cost estimates were made by computer simulation alone. The first simulations were based only on the physical properties incorporated in the software data bank. In a second step additional physical properties mostly liquid liquid equilibrium (LLE) data were measured in order to increase the accuracy of the simulation of the most critical steps. First screening experiments of pervaporation to eliminate water and polar impurities such as methanol and ethanol from the tetrahydrofuran (THF) mixtures were stopped early, as it appeared that the alternatives based on counter current extraction (CCE) and rectification alone were less expensive and probably more robust. The most promising processes were piloted. The pilot experiments allowed confirmation of the results of the simulations and allowed the simulations to be updated to reflect the pilot results. A large part of the work during the pilot experiments was to verify the behaviour of further impurities contaminating the solvents, which had not been taken into account in the first screening. All impurity substances had to be purged efficiently, so that they would not accumulate after repeated recoveries of the solvents. 

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