A thermodynamic study of ketoreductase-catalyzed reactions 4. Reduction of 2-substituted cyclohexanones in n-hexane

The equilibrium constants K for the ketoreductase-catalyzed reduction reactions (2-substituted cyclohexanone + 2-propanol = cis- and trans-2-substituted cyclohexanol + acetone) have been measured in n-hexane as solvent. The 2-substituted cyclohexanones included in this study are: 2-methylcyclohexanone, 2-phenylcyclohexanone, and 2-benzylcyclohexanone. The equilibrium constants K for the reactions with 2-methylcyclohexanone were measured over the range T = 288.15 to 308.05 K. The thermodynamic quantities at T = 298.15 K are: K = (2.13 ± 0.06); ${\mathrm{\Delta }}_{\text{r}}{G}_{\text{m}}^{\circ }=-(1.87\pm 0.06)\text{kJ}·{\text{mol}}^{-1}$; ${\mathrm{\Delta }}_{\text{r}}{H}_{\text{m}}^{\circ }=-(6.56\pm 2.68)\text{kJ}·{\text{mol}}^{-1}$; and ${\mathrm{\Delta }}_{\text{r}}{S}_{\text{m}}^{\circ }=-(15.7\pm 9.2)\text{J}·{\text{K}}^{-1}·{\text{mol}}^{-1}$ for the reaction involving cis-2-methylcyclohexanol, and K = (10.7 ± 0.2); ${\mathrm{\Delta }}_{\text{r}}{G}_{\text{m}}^{\circ }=-(5.87\pm 0.04)\text{kJ}·{\text{mol}}^{-1}$; ${\mathrm{\Delta }}_{\text{r}}{H}_{\text{m}}^{\circ }=-(2.54\pm 1.8)\text{kJ}·{\text{mol}}^{-1}$; and ${\mathrm{\Delta }}_{\text{r}}{S}_{\text{m}}^{\circ }=(11.2\pm 6.4)\text{J}·{\text{K}}^{-1}·{\text{mol}}^{-1}$ for the reaction involving trans-2-methylcyclohexanol. The standard molar Gibbs free energy changes ${\mathrm{\Delta }}_{\text{r}}{G}_{\text{m}}^{\circ }$ for the reactions (trans-2-substituted cyclohexanol = cis-2-substituted cyclohexanol) in n-hexane have also been calculated and compared with the literature data that pertain to reactions in the gas phase and at higher temperatures. Experiments carried out with a chiral column demonstrated that the enzymatic reduction of 2-phenylcyclohexanone catalyzed by the ketoreductase used in this study is not stereoselective.     

A study of the synthesis and some reactions of 3-phenyl-1,4-benzothiazines

Condensation of o-aminothiophenol with 2-bromoacetophenone yields 3-phenyI-1,4-benzo-thiazine hydrobromide, which upon treatment with alkali gave a mixture of 3-phenyl-2H-1,4-benzothiazine (VIIa) and 3-phenyl-4H-1,4-benzothiazine (VIIb). Catalytic hydrogenation led to rearrangement of the benzothiazine (VIIa) to 2-phenyl-2-methyl-2,3-dihydrobenzothiazole (X), while reduction with lithium aluminium hydride resulted in 3-phenyl-2,3-dihydro-4H-1,4-benzothiazine (XVI). The latter was transferred to 3-phenyl-4-aminoalkyl-2,3-dihydro-4H-1,4-benzothiazines (XVII and XVIII).     

Flash photolysis of flavins. I. Photoreduction in non-aqueous solvents

Abstract— The photoreduction of riboflavin, FMN, and lumiflavin in a series of hydroxylic solvents has been examined using flash photolysis. A comparison of the relative quantum yields for the photoxidation of several alcohols and esters by lumiflavin demonstrated that the hydroxyl hydrogen of the alcohol is abstracted approximately twice as readily as is the alpha hydrogen. The use of glycerol as both solvent and reductant provided direct evidence that the initial reaction proceeds by a one-electron reduction to form the flavin semi-quinone. In the case of riboflavin (and FMN) the kinetic results are consistent with an initial intramolecular hydrogen atom transfer, analogous to photobleaching in aqueous solution, followed by a reaction of the semi-quinone with the reductant which prevents degradation of the ribityl side-chain. Quenching by iodide indicates that all the reactions proceed via the flavin triplet state, as is the case in aqueous systems.     

The enhancement of acidity in non-aqueous solvents

Summary The acid strength of short-chain carboxylic acids in acetonitrile and acrylonitrile can, by addition of anhydrous alkaline earth perchlorates, be enhanced sufficiently to permit titration of the acid with a tertiary amine in the presence of acid anhydride. This salt effect has been studied by means of potentiometric and automatic thermometric titrations and two distinct mechanisms are thought to be involved: a metathetical reaction at low salt concentrations and a proton desolvation effect at high salt concentrations. High-resolution infra-red spectroscopy has been used to assess the extent of sol vent-cation interaction in acetonitrile. Several equations are used to describe the probable interactions taking place in such salt enhancement phenomena.

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Steigerung der Acidität in nichtwärigen Lösungsmitteln

Zusammenfassung Der Säuregrad von kurzkettigen Carbonsäuren in Acetonitril und Acrylnitril kann durch Hinzufügen von wasserfreien Perchloraten der Erdalkalien genügend gesteigert werden, um bei Vorhandensein von Säureanhydrid eine Titration der. Säure mit einem tertiären Amin zu ermöglichen. Dieser Salzeffekt wurde mit Hilfe von potentiometrischen und automatischen thermometrischen Titrationen untersucht, und es wird angenommen, daß dabei zwei verschiedene Vorgänge eine Rolle spielen: eine Austauschreaktion bei schwachen und ein Desolvatationseffekt bei hohen Salzkonzentrationen. Zur Beurteilung des Ausmaßes der Wechselwirkung zwischen Lösung und Kation in Acetonitril wurde die Infrarot-Spektroskopie mit hoher Auflösung benutzt. Die wahrscheinlich stattfindenden Reaktionsvorgänge werden anhand verschiedener Gleichungen beschrieben.

Lecture presented at Euroanalysis I Conference, 28.8.–1. 9. 1972 in Heidelberg, Germany.     

Coulometric titration of acids in non-aqueous solvents

Coulometric titrations of mineral acids, sulphonic acids, carboxylic acids, enols, imides and phenols have been carried out in t-butanol or in acetone with electrically generated tetrabutylammonium hydroxide. Either a potentiometric titration or a visual indicator end-point may be used. The amount of acid titrated ranges from 10 to 60 muequiv, and the precision and accuracy of the method are excellent.     

Titration of thiol groups in non-aqueous solvents

Thiols are titrated in acetone or dimethylformamide with sodium methoxide, employing visual end-point detection with Thymol Blue, Victoria Blue, p-hydroxyazobenzene or Azo Violet. Aromatic thiols are titrated in the presence of aliphatic thiols in acetone, with Thymol Blue as indicator.     

Kinetic-catalytic determination of vanadium in non-aqueous solvents

Determination of trace vanadium in organic solvents is studied by use of the oxidation of o-dianisdine with t-butyl hydroperoxide. The sensitivity of the catalyzed reaction is optimized by application of a modified simplex method. Under optimum conditions the detection limit is 0.7 ng V ml^?1 in acetonitrile and the relative standard deviation is 0.048. The effect of other metal ions and of co-solvents is discussed. The method is used for trace determinations of vanadium in organic solvents of high purity.     

Polarographic reduction of hydrogen ion in non-aqueous solvents

The polarographic reduction of hydrogen ion, furnished by dissociation of a Brønsted acid or present in the undissociated Brønsted acid, is reviewed for the situation where a solvent other than water is involved.     

Electrochemical studies of complex fluorides in non-aqueous solvents

Electrochemical studies on hydrolytically unstable complex fluorides have been shown to be possible in highly purified acetonitrile. The techniques of study will be described briefly. A survey of the results obtained to date wille given.MoF₆ is a stronger oxidising agent than WF₆ by 1.06 volts. Neither |MoF₆|^? nor |WF₆|^? can be reduced below |MF₆|^? in acetonitrile. |UF₆|^? can be reduced to the transient species |UF₆|^2? which is unstable in solution. |OsF₆|^? undergoes successive reduction to |OsF₆|^2? and |OsF₆|^3?.|MF₆L|^? undergoes complex electrochemical behaviour involving reduction to |MF₆L|^2? with subsequent dissociation to |MF₆|^? and L^?. Reoxidation is in the presence of L^? and hence none of the redox steps are fu]ly reversible. The relation between the electrode potentials and the ligand L will be discussed.We thank NATO for a grant in support of this work.     

Alkaline errors of glass electrodes in non-aqueous solvents

Alkaline errors of glass electrodes in isopropanol were obtained from a comparison with the hydrogen electrode. Electrode glasses which show low alkaline errors in water are also more ideal in isopropanol. Univalent metal ions cause larger deviations than bivalent. Hysteresis effects were found in going from alkaline to acid solutions but not for the reverse direction.     

The non-aqueous reactions of some 1,4-benzodiazepines.

The data presented for the behavior of 3-hydroxy-1,4-benzodiazepines during non-aqueous titrations indicate that: (a) the First stage protonation during titration as a base with perchloric acid occurs at the N—4 position and is relatively unaffected by substitution at the 3-position, except when the substituent is electron-withdrawing; (b) deprotonation during titration as an acid with tetrabutylammonium hydroxide occurs at the N-1 position rather than at the 3-OH substituent; (c) the similarity of the u.v. spectra of neutral and basic solutions of lorazepam indicate that a tautomerism in basic solution postulated previously does not occur to any great extent; and (d) titration with tetrabutylammonium hydroxide should be acceptable as an assay method tor lorazepam.     

Nucleophilic reactions of 1-methyl-2-methoxy-2-phenyl-3-oxo-2,3-dihydroindole

The title compound (1) was prepared via methylene blue (MB)-sensitized photooxy-genation of l-methyl-2-phenylindole (2d) in methanol. Acid-catalyzed nucleophilic substitution of 1 with nucleophiles gave 1,2,2-trisubstituted 3-oxo-2,3-dihydroindoles (3-6). Reduction of 1 with lithium aluminum hydride, followed by acidic workup yielded 4d and 2d, whereas the same reduction reaction of 1, followed by neutral workup gave l-methyl-2-phenyl-3-hydroxy-2,3-dihydroindole (15), together with 3. The reaction pathways of nucleophilic substitution and reduction of 1 were discussed.     

New cycloaddition reactions of 1-phenyl-4-vinylpyrazole

1-Phenyl-4-vinylpyrazole reacts with methyl propiolate and N-phenylmaleimide giving via the Diels-Alder 1:1 adducts, products (4) and (8), and also the 1:2 adducts (5), (6) and (9) resulting from an “ene” reaction of the initially forced cycloadducts. The obtention of the adducts (5) and (6) in equimolecular amounts is a good example of the non-regioselective character of the “ene” reaction. The reaction with tetracyanoethylene takes place through the olefinic substituent giving the π² + π² adduct (10).