Formamide-dioxan mixtures

Likewise, the strucmre of subtilisin (pH 3.0) suspended in varying ratios of acetonitrile and water demonstrated a-helical content similar to that in the lyophilized powder (Griebenow and Klibanov, 1996). Furthermore, the rate of transesteriflcation reactions of subtilisin (pH 7.8) suspended in DMSO/acetonitrile, formamide/acetonitrile or formamide/dioxane were increased approximately 100-fold over aqueous conditions (Almarsson and Klibanov, 1996). Similar results were obtained for subtilisin (pH 7.8) in a tetrahydrofuran/1-propanol mixture (Affleck et al., 1992). These results can be attributed to the increased structural rigidity of the active conformation of the protein in the solid, and the denaturing characteristics of the solvent at the solvent-particulate interface. Preservation of this molecular memory or molecular imprint of the protein can also be used to stabilize structure and activity (Mishra et al., 1996 Rich and Dordick, 1997 Santos et al., 2001). Subtilisin was lyophilized from crown ethers, resulting in more native like structure, by FTIR, and increased enzyme activity in THF, acetonitrile and dioxane (Santos et al.,2001). 

Fig. 5.3.4. Dependence of log Ka on for electrolytes in solvent mixtures. O, CsBr in water-tetrahydroftiran (n = A, CsBr in water-dioxan (n = , MgS04 in formamide-dioxan...

An interesting observation reported in Table XLIX is the increase in the hydroquinone/catechol ratio from 1.44 to 1.99 when the dielectric constant of the medium is decreased from 58.9 to 39.2 by addition of methanol to water. A similar increase in the hydroquinone/catechol ratios was also observed in phenol hydroxylation catalyzed by TS-1 (266) in dioxane-water and tert-butyl alcohol-water mixtures. The para/ortho ratio increased nearly 10-fold when 10% dioxane was added to water. Similarly, the para/ortho ratio more than doubled (1.3-3.0) when 10% tert-butyl alcohol was added to water. An opposite trend, namely, a decrease in the para/ortho ratio from 1.4 to 0.6, was observed when 10% formamide (s = 108) was added to water. Because of geometric constraints in the MFI pores, catechol is expected to be formed more easily on the external surface of TS-1 crystallites than in the pores (91). Hydroquinone, less spatially demanding, can form in the TS-1 channels. A greater coverage of the hydrophobic... 

The first novel casting solution to be investigated consisted of THF and formamlde, a pair of non-solvents combined to serve as a cosolvent system. This system was selected because by simply varying the proportions of the two liquids it has the ability to dissolve SPSF-Na of all degrees of sulfonatlon under the desired conditions (15 wt-% polymer, 25°C) In a similar manner, dioxane-formamide mixtures may be employed. 

Variation of the fluorine-19 chemical shift on association has been used to determine solvent effects and basicities28. Muller29 has examined the chemical shifts of 6,6,6-trifluoro-l-hexanol (TFH) in mixtures of water and organic liquids such as acetone, dioxane, THF, ethylene glycol, 2-methoxyethane, 1,2-dimethoxyethane, methanol, r-butanol, dimethyl-formamide and dimethyl sulphoxide. Typical plots are shown in Figures 2 and 3. Solvents... 

Electromotive force measurements of HC1 solutions in pure NMA and in NMA/dioxane solvent mixtures using the silver-silver chloride electrode have been reported by Dawson and his co-workers (1,2,3). The only other potentiometric studies in a solvent of dielectric constant higher than that of water appear to have been in formamide (6,7,8,9, 10) and in N-methylpropionamide (NMP) (11,12,13,14,15). 

A powerful oxidizer. Explosive reaction with acetaldehyde, acetic acid + heat, acetic anhydride + heat, benzaldehyde, benzene, benzylthylaniUne, butyraldehyde, 1,3-dimethylhexahydropyrimidone, diethyl ether, ethylacetate, isopropylacetate, methyl dioxane, pelargonic acid, pentyl acetate, phosphoms + heat, propionaldehyde, and other organic materials or solvents. Forms a friction- and heat-sensitive explosive mixture with potassium hexacyanoferrate. Ignites on contact with alcohols, acetic anhydride + tetrahydronaphthalene, acetone, butanol, chromium(II) sulfide, cyclohexanol, dimethyl formamide, ethanol, ethylene glycol, methanol, 2-propanol, pyridine. Violent reaction with acetic anhydride + 3-methylphenol (above 75°C), acetylene, bromine pentafluoride, glycerol, hexamethylphosphoramide, peroxyformic acid, selenium, sodium amide. Incandescent reaction with alkali metals (e.g., sodium, potassium), ammonia, arsenic, butyric acid (above 100°C), chlorine trifluoride, hydrogen sulfide + heat, sodium + heat, and sulfur. Incompatible with N,N-dimethylformamide. 

In a usually less favorable procedure formamide acetals (437 equation 204) are accessible from chloroform or trichloroacetic acid esters and mixtures of secondary amines and alkoxides - dichlorocar-bene is thought to be an intermediate. Chloromethoxycarbene, generated from the diazirine (438 equation 205) inserts into the NH bond of diethylamine to yield the amide acetal (439). The undissociated a,a-difluorotrialkylamines (440 Scheme 80) react with the alkali metal salts of diols to afford 1,3-dioxanes or l,3-dioxolMes7 - Noncyclic amide acetals can be prepared in the same manner. 

The apparent acid dissociation constants (p s)Ka) of two water-insoluble drugs, ibuprofen and quinine, were determined pH-metrically in ACN water, dimethyl-formamide water, DMSO water, 1,4-dioxane-water, ethanol water, ethylene glycol-water, methanol water, and tetrahydrofuran water mixtures. A glass electrode calibration procedure based on a four-parameter equation (pH = alpha-i- SpcH -i-jH[H+] -i-jOH[OH ]) was used to obtain pH readings based on the concentration scale (pcH). We have called this four-parameter method the Four-Plus technique. The Yasuda Shedlovsky extrapolation p s)K a + log [H2O] = A/epsllon -1- B) was used to derive acid dissociation constants in aqueous solution (pKa). It has been demonstrated that the pK a values extrapolated from such solvent-water mixtures are consistent with each other and with previously reported measurements. The suggested method has also been applied with success to determine the pKa values of two pyridine derivatives of pharmaceutical Interest. Spectrometric, ultraviolet (UV) ... 

Preparation ofS [1] A solution of N-(tert-butyloxy)carbonyliminodiacetic acid (1) (0.349 g, 1.50 mmol) in dimethyl formamide (DMF) (15 ml) was treated with N -(3-dimefhylaminopropyl)-N-ethyl-carbodiimide hydrochloride (EDC) (0.294 g, 1.54 mmol) at 25 °C. The mixture was stirred at 25 °C for 1 h, and then the amine (1 equiv.) was added and the reaction mixture was stirred for 20 h. It was then poured into 10% aqueous HCl (60 mL) and extracted with ethyl acetate (100 mL). The organic phase was washed with 10% HCl (40 mL) and saturated aqueous NaCl (2 x 50 mL), dried (NazSOr), filtered, and concentrated in vacuo to yield the diacid monoamides 2. Each of the diacid monoamides 2 was dissolved in anhydrous DMF (20 mL/mmol) and the solutions obtained were divided into three equal portions in three separate vials. Each solution was then treated with one of the three amines (1 equiv.), diisopropylefhylamine (2 equiv.), and (benzotriazol-l-yloxy)tripyr-rolidinophosphonium hexafluorophosphate (PyBOP) (1 equiv.). Each solution was stirred at 25 °C for 20 h. The respective mixture was then poured into 10% HCl and extracted with ethyl acetate. The organic phase was washed sequentially with 10% HCl, saturated aqueous NaCl, 5% aqueous NaHCOs, and further saturated aqueous NaCl, then dried (Na2SO4), filtered, and concentrated to yield the diamides 3. Each of the diamides 3 was dissolved in 4 N HCl/dioxane (32 mL/mmol) and the respective mixture was stirred at 25 °C for 45 min. The solvent was then removed in vacuo, the residue was dissolved in anhydrous DMF (28 mL/mmol), and the solution obtained was divided into three equal portions, which were placed in three separate vials. Each solution was treated with one of three carboxylic acids (1 equiv.) followed by diisopropylamine (3 equiv.) and PyBOP (1 equiv.) and the mixtures were stirred for 20 h. Each mixture was then poured into 10% HCl and extracted with ethyl acetate. The organic phase was washed sequentially with 10% HCl, saturated aqueous NaCl, 5% aqueous NaHCOs, and further saturated aqueous NaCl, then dried (Na2SO4), filtered, and concentrated in vacuo to yield the final products 5. 

Preparation of the resin Polystyrene-divinylbenzene (1%) copolymer 21 (Fluka) was washed [71] to removed shorter polystyrene components and remaining monomers and reagents with each of the following solutions at 60-80°C for 30-60 min NaOH (1 N), HCl (1 N), NaOH (2 N)-dioxane (1 2), HCl (2 N)-dioxane (1 20, water, dimethyl formamide (DMF). The resin was then washed at room temperature with HCl (2 N) in methanol, water, methanol, methanol-dichloromethane (1 3), and methanol-dichlo-romethane (1 10) and the resin was dried at 50-70°C under reduced pressure. The washed polystyrene resin (13 g) was suspended under nitrogen in anhydrous cyclohexane (80 mL) in a 250-mL polymer synthesis flask. Tetra-methylethylenediamine (TMEDA, 20 mL, 132.5 mmol) and n-butyllithium (2.0 M in cyclohexane, 80 mL, 160 mmol) were successively added and the mixture was stirred at 65°C for 4 h. The dark burgundy-colored resin was filtered under nitrogen and washed with anhydrous cyclohexane (2 X 100... 

Ionic solvation in H2O + cosolvent mixtures has been the subject of a number of recent communications. Cosolvents have included acetone, form-amide, NN-dimethylformamide, NN-dimethylacetamide, t-butyl alcohol, " and dioxan. Interpretation of H n.m.r. data (173—303 K) for solutions of Be(N03)2 in aqueous acetone solutions has shown that Be is present mainly in the form of tetra-aquo complexes, coexisting with (probably) polymerized hydroxo(oxo)diaquo complexes. The existence of the tetra-aquo complex has been confirmed by analyses of n.m.r. spectra of aqueous Be(N03)2 solutions. The formation of solvated cationic species in HaO+formamide (Na ) and H2O + DMF (Li" ", Na" ", mixtures has also been investigated in a study of the... 

Yellin and Marcus [Ma 74, Ye 72, Ye 74] used Raman spectroscopy to examine interactions of this type. They studied the interactions of cadmium(II) and mercury(II) halides and cyanides with water and with various organic solvents, such as alcohols, acetone, dioxane, acetonitrile, formamide, dimethylformamide, N-ethylacetamide, dimethylacetamide and mixtures of these. 

Solubility considerations frequently dictate the use of solvents other than pure water for organic voltammetry aqueous mixtures containing varying amounts of such miscible solvents as glycols, dioxane, acetonitrile, alcohols, Cellosolve, or acetic acid have been used. Anhydrous media such as acetic acid, formamide, di-ethylamine, and ethylene glycol have also been investigated. Supporting electrolytes are often lithium or tetraalkyl ammonium salts. 

---