Phase base-free neutral

Base-Free Neutral Phase-Transfer Reaction... 

Although quaternary onium bromides and chlorides as phase-transfer catalysts are generally beUeved to require base additives for phase-transfer reactions of active methylene and methine compounds, which were discussed above, we have recently discovered an hitherto unknown base-free neutral phase-transfer reaction system in asymmetric conjugate additions (Scheme 14.5) [23]. The reactions were efficiently promoted by chiral bifunctional ammonium bromide (S)-7 under neutral conditions with water-rich biphasic solvent. The role of hydroxy groups in the bifunctional catalyst was clearly shown in the transition-state model of the reaction based on the single-crystal X-ray structure of ammonium amide [23b] and nitro-nate [23c]. 

Recently, Maruoka and coworkers presented an asymmetric aldol reaction of a-substituted nitroacetates with aqueous formaldehyde under base-free neutral phase-transfer conditions [127]. In the presence of 0.1mol% (S)-43a, the aldol products were obtained in 62-86% yield with 74-91% ee (Scheme 12.21). Two of the aldol products were treated with zinc and acetic acid in isopropanol to give the corresponding a-methylserinates 96, which are core structure of biologically active natural products such as conagenin and piperazimycins. 

Figure 8-40. Analysis of Product M (free base) as neutral species using two types of volatile buffers. Chromatographic conditions Column Luna C8(2) 150 x 4.6 mm. Mobile phase Aqueous (see A and B for exact conditions), acetonitrile. Wavelength, 247 nm column temperature, 40°C flow, 1 mL/min injection volume, 10 pL. Linear gradient from 5% acetonitrile to 95% acetonitrile over 20 min, with 3-min hold at 95% acetonitrile.

While selective complexation makes the membrane more permeable to the analyte ion than the co-ions, selectivity against counter ions in neutral-ionophore-based membranes is achieved by ionic sites, not by the ionophore. In fact, the ionophore-analyte complexation decreases the free analyte activity in tlie membrane to enhance the salt extraction into the membrane phase, which may result in counter-ion interference due to Donnan exclusion failure (7). Although the PVC matrix has inherent negative sites as an impurity (11), the concentration is so low that the anionic sites were initially introduced in cation-selective ISEs based on neutral ionophores to suppress the counter-ion interference (12). 

Weak base resins when in the free base (hydroxyl) form are not capable of splitting neutral salts such as sodium chloride. Salt forms of weak base resins release anions to the Hquid phase if other ions for which the resin has a greater selectivity are present. 

A mixture of 31 5 g (0.1 mol) of 2-chloro-9-(3 -dimethylaminopropylidene)-thiaxanthene (MP 97°C) and 100 g of N-( 3-hydroxyethyl)-piperazine is heated to 130°C and boiled under reflux at this temperature for 48 hours. After cooling, the excess of N-( 3-hydroxyethyl)-piperazine Is evaporated in vacuo, and the residue is dissolved in ether. The ether phase is washed with water and extracted with dilute acetic acid, and 2-chloro-9-[3 -N-(N - -hydroxy-ethyD-piperazinylpropylidene] -thiaxanthene separated from the aqueous acetic acid solution by addition of dilute sodium hydroxide solution to basic reaction. The free base is extracted with ether, the ether phase dried over potassium carbonate, the ether evaporated and the residue dissolved in absolute ethanol. By complete neutralization of the ethanolic solution with a solution of dry hydrogen chloride in absolute ethanol, the dihydrochloride of 2-chloro-9-[3 -N-(N -(3-hydroxyethyl)-piperazinylpropylidene] -thiaxanthene is produced and crystallizes out as a white substance melting at about 250°C to 260°C with decomposition. The yield is 32 g. 

Some highly hydrophobic weak acids and bases exhibit substantial hydro-phobicity even in the ionized state. For highly hydrophobic ionogenic organic compounds, not only is transfer of the neutral species between the aqueous phase and the immiscible phase important, but the transfer of the hydrophobic, ionized, organic species as free ions or ion pairs may also be significant [37]. Mathematically, this is described by refining the n-octanol/ water partition coefficient, as defined in equation (2.7), to reflect the pH-dependent distribution between water (W) and K-octanol (O) of chemical X in both the ionized and nonionized forms. If chemical X is a weak acid, HA, the distribution ratio is... 

A mixture of 100 kg of 8-benzyltheophilline, 36 L of N-ethylethanolamine, 300 L of 1,2-dichlorethane and 71 kg of sodium carbonate was refluxed for 24 hours. Then 36 L of N-ethylethanolamine was added and the reaction mixture was refluxed. After cooling to the mixture was added the water and hydrochloric acid. The organic phase was extracted with hydrochloric acid. The acidic phase was neutralized with sodium carbonate and the 7-(N-ethyl-N-p-hydroxyethylaminoethyl)-8-benzyltheophilline was extracted with dichloromethane. The solvent was evaporated and the free base of 7-(N-ethyl-N-p-hydroxyethylaminoethyl)-8-benzyltheophilline was dissolved in methanol. Hydrochloride of 7-(N-ethyl-N-p-hydroxyethylaminoethyl)-8-benzyltheophilline was obtained by addition to the solution the hydrochloric acid yield 81%, melting point 185-186°C. 

Monomeric Ce(tritox)3 was claimed in 1989 [29]. However, the structure determination was hampered by disordering problems both in solvent-free Ce(tritox)3 and Nd(tritox)3(THF) [36]. Appropriate crystallization conditions were borrowed from cyclopentadienyl chemistry. The corresponding LnCp3 systems show remarkable crystallization behavior in the presence of neutral bases like acetonitrile and DMSO which impose polarities into the molecule [37], Indeed, this phenomenon could be transferred to Nd(tritox)3 in a 2-phase system n-pentane/acetonitrile at — 35°C [38], X-ray analysis revealed a monomeric alkoxide of formula Nd(tritox)3(NCCH3)2 with a trigonal bipyramidal geometry at the neodymium center (Fig. 2, Table 1). The alkoxide O-atoms and... 

Under neutral conditions, the positional reactivity order for the halogenation of quinoline appears to be 3 > 6 > 8, whereas isoquinoline gives mainly 4-substitution. For isoquinoline, the fact that reaction occurs on the free base is adequate explanation for the change in orientation, since, contrary to common belief, the 4-position is shown by calculations and gas-phase studies of reactivity to be the most reactive in the neutral isoquinolines (see Section U.G.) indeed, more reactive than benzene. 

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