Temperature racemic

The hydrogenation of methyl pyruvate proceeded over 4% Pd/Fe20 at 293 K and 10 bar when the catalyst was prepared by reduction at room temperature Racemic product was obtained over utunodified catalyst, modification of the catalyst with a cinchona alkaloid reduced reaction rate and rendered the reaction enantioselective. S-lactate was formed in excess when the modifier was cinchonidine, and R-lactate when the modifier was cinchonine... 

Whereas the rapidly equilibrating mixture of diastereomers 63 B,B was optically stable at room temperature, racemization occured when solutions in toluene were heated for several hours. A kinetic study revealed a racemization barrier of AG 8 = 27.6 2 (115.7. + 8.2) kcal(kJ)/mol, for which high energy Berry processes running through the decisive, achiral trigonal-bipyramidal transition states 66, 67 with diequatorial 2,2 -biphenylylene ligands were made responsible 74). Equivalent... 

In a field closely related to biphenyl, hindered rotation around the pyridyl-amide bond allowed the resolution of the nicotinamide analogue 142 into enantiomers. Compound 142 was optically stable at 25°C in water at higher temperatures racemization occurs (e.g., t1/2 = 3.1 hr at 100°C) (82RTC191 ... 

Neutral half-sandwich complexes of the form [Cp Ru(NHC)Q] have been employed m the racemization of chiral alcohols [79]. The combination of 5mol% ruthenium complex and 5mol% NaO Bu allowed the room temperature racemization of (S)-l-phenylethanol in quantitative yield in 30 min in toluene in the case of the ICy derivative. Activity proved to be a function of the NHC, decreasing in the order ICy>lPr>lAd, which correlated with increasing steric demand (calculated %Vbur values of 25.6, 31.2, and 34.0, respectively). Other alcohols were effective with yields of the racemic forms of (5)-2-naphthylethanol, (R)-4-chlorophenylethanol, and even (S)-octan-3-ol... 

The alkyl azide 118 is reduced to a primary amine by the Pd on carbon-catalyzed reaction of ammonium formate in MeOH at room temperature. No racemization takes place with chiral azides[l 11,112]. 

Structures A and A are nonsuperimposable mirror images of each other Thus although as 1 2 dichloro cyclohexane is chiral it is optically inactive when chair-chair interconversion occurs Such interconver Sion IS rapid at room temperature and converts opti cally active A to a racemic mixture of A and A Because A and A are enantiomers interconvertible by a conformational change they are sometimes re ferred to as conformational enantiomers... 

Trigonal pyramidal molecules are chiral if the central atom bears three different groups If one is to resolve substances of this type however the pyramidal inversion that mterconverts enantiomers must be slow at room temperature Pyramidal inversion at nitrogen is so fast that attempts to resolve chiral amines fail because of their rapid racemization... 

Section 7 16 Atoms other than carbon can be chirality centers Examples include those based on tetracoordmate silicon and Incoordinate sulfur as the chirality center In principle Incoordinate nitrogen can be a chirality center m compounds of the type N(x y z) where x y and z are different but inversion of the nitrogen pyramid is so fast that racemization occurs vrr tually instantly at room temperature... 

Physical Properties. When crystaUized from aqueous solutions above 5°C, natural (R-R, R )-tartaric acid is obtained in the anhydrous form. Below 5°C, tartaric acid forms a monohydrate which is unstable at room temperature. The optical rotation of an aqueous solution varies with concentration. It is stable in air and racemizes with great ease on heating. Some of the physical properties of (R-R, R )-tartaric acid are Hsted in Table 7. 

In the United States and some European countries, beet-sugar-waste molasses, or Stefen s waste, has been used as raw material for MSG production. The 2-pyrrohdinone-5-carboxyhc acid [98-79-3] contained ia beet sugar as by-product, is hydrolyzed at weakly alkaline pH, and moderate temperature (eg, pH 10.5—11.5, at 85°C for 2 h) to avoid racemization (14). The pH of the hydrolyzate is adjusted to 3.2 with a mineral acid to precipitate crystals of L-glutamic acid. The L-glutamic acid crystals obtained are transformed to MSG as described above. 

An hplc assay was developed suitable for the analysis of enantiomers of ketoprofen (KT), a 2-arylpropionic acid nonsteroidal antiinflammatory dmg (NSAID), in plasma and urine (59). Following the addition of racemic fenprofen as internal standard (IS), plasma containing the KT enantiomers and IS was extracted by Hquid-Hquid extraction at an acidic pH. After evaporation of the organic layer, the dmg and IS were reconstituted in the mobile phase and injected onto the hplc column. The enantiomers were separated at ambient temperature on a commercially available 250 x 4.6 mm amylose carbamate-packed chiral column (chiral AD) with hexane—isopropyl alcohol—trifluoroacetic acid (80 19.9 0.1) as the mobile phase pumped at 1.0 mL/min. The enantiomers of KT were quantified by uv detection with the wavelength set at 254 nm. The assay allows direct quantitation of KT enantiomers in clinical studies in human plasma and urine after adrninistration of therapeutic doses. 

Alcohol dehydrogenase-catalyzed reduction of ketones is a convenient method for the production of chiral alcohols. HLAD, the most thoroughly studied enzyme, has a broad substrate specificity and accommodates a variety of substrates (Table 11). It efficiendy reduces all simple four- to nine-membered cycHc ketones and also symmetrical and racemic cis- and trans-decalindiones (167). Asymmetric reduction of aUphatic acycHc ketones (C-4—C-10) (103,104) can be efficiendy achieved by alcohol dehydrogenase isolated from Thermoanaerohium hrockii (TBADH) (168). The enzyme is remarkably stable at temperatures up to 85°C and exhibits high tolerance toward organic solvents. Alcohol dehydrogenases from horse Hver and T. hrockii... 

Diaziridines also show slow nitrogen inversion, and carbon-substituted compounds can be resolved into enantiomers, which typically racemize slowly at room temperature (when Af-substituted with alkyl and/or hydrogen). For example, l-methyl-3-benzyl-3-methyl-diaziridine in tetrachloroethylene showed a half-life at 70 °C of 431 min (69AG(E)212). Preparative resolution has been done both by classical methods, using chiral partners in salts (77DOK(232)108l), and by chromatography on triacetyl cellulose (Section 5.08.2.3.1). 

To minimize racemization, the use of nonpolar solvents, a minimum of base, low reaction temperatures, and carbamate protective groups (R = O-alkyl or O-aryl) is effective. (A carbamate, R = O-r-Bu, has been reported to form an oxazolone that appears not to racemize during base-catalyzed coupling.) ... 

The present method, based on a recent publication, ensures a low temperature of reaction which precludes racemization and is more convenient than the fusion method for large-scale operation. 

Although unsynunetrically substituted amines are chiral, the configuration is not stable because of rapid inversion at nitrogen. The activation energy for pyramidal inversion at phosphorus is much higher than at nitrogen, and many optically active phosphines have been prepared. The barrier to inversion is usually in the range of 30-3S kcal/mol so that enantiomerically pure phosphines are stable at room temperature but racemize by inversion at elevated tempeiatuies. Asymmetrically substituted tetracoordinate phosphorus compounds such as phosphonium salts and phosphine oxides are also chiral. Scheme 2.1 includes some examples of chiral phosphorus compounds. 

Whereas the barrier for pyramidal inversion is low for second-row elements, the heavier elements have much higher barriers to inversion. The preferred bonding angle at trivalent phosphorus and sulfur is about 100°, and thus a greater distortion is required to reach a planar transition state. Typical barriers for trisubstituted phosphines are BOSS kcal/mol, whereas for sulfoxides the barriers are about 35-45 kcal/mol. Many phosphines and sulfoxides have been isolated in enantiomerically enriched form, and they undergo racemization by pyramidal inversion only at high temperature. ... 

To minimize racemization, the use of nonpolar solvents, a minimum of base, low-reaction temperatures, and carbamate protective groups (R = O-alkyl or O-aryl) are effective. 

Racemization has been reported to occur in some Bischler-Napieralski reactions of 1-substituted phenethylamides. However, this racemization can be suppressed by conducting the reactions at lower temperatures (0 °C-rt). For example, the product 49 obtained in reaction of 48 with P2O5 at 140 °C was found to be racemic, whereas the product obtained from a reaction conducted at room temperature retained optical activity. ... 

Optical activity owing to restricted rotation (atropisomerism) has been demonstrated in two phenylthiophenes 2-(6-methyl-2-nitro-phenyI)-3-thiophenecarboxylic acid (41), which rapidly racemized in solution, and 2,5-dimethyl-4- (6 -methyl-2 -nitrophenyl) 3-thio-phenecarboxylic acid (42), which was optically stable (at room temperature). Recently the first bithienyl, 2,2 -dicarboxy-4,4 -dibromo-5,5 -dimethyl-3,3 -bithienyl (43), has been resolved into optical anti-podes which were optically stable. 

Racemic or optically active perhydropyrido[l,2-a]pyrazines were obtained by reduction of 9a5-perhydropyrido[l,2-u]pyrazin-4-one with LAH in Et20 at room temperature (99H(51)2065) and by reduction of perhydropyr-ido[l,2-u]pyrazine-l,4-diones with LAH in boiling THF (97USP5703072, 00JAP(K)00/86659). Treatment of (9uS)-2-(fcrf-butoxycarbonyl)perhydro-pyrido[l,2-u]pyrazin-4-one with LAH in Lt20 afforded (9uS)-2-fcrf-butox-ycarbonyl-l,6,7,8,9,9a-hexahydro-2//-pyrido[l,2-a]pyrazine (99H(51)2065). 

Among the J ,J -DBFOX/Ph-transition(II) metal complex catalysts examined in nitrone cydoadditions, the anhydrous J ,J -DBFOX/Ph complex catalyst prepared from Ni(C104)2 or Fe(C104)2 provided equally excellent results. For example, in the presence of 10 mol% of the anhydrous nickel(II) complex catalyst R,R-DBFOX/Ph-Ni(C104)2, which was prepared in-situ from J ,J -DBFOX/Ph ligand, NiBr2, and 2 equimolar amounts of AgC104 in dichloromethane, the reaction of 3-crotonoyl-2-oxazolidinone with N-benzylidenemethylamine N-oxide at room temperature produced the 3,4-trans-isoxazolidine (63% yield) in near perfect endo selectivity (endo/exo=99 l) and enantioselectivity in favor for the 3S,4J ,5S enantiomer (>99% ee for the endo isomer. Scheme 7.21). The copper(II) perchlorate complex showed no catalytic activity, however, whereas the ytterbium(III) triflate complex led to the formation of racemic cycloadducts. 

Enantioselectivities were found to change sharply depending upon the reaction conditions including catalyst structure, reaction temperature, solvent, and additives. Some representative examples of such selectivity dependence are listed in Scheme 7.42. The thiol adduct was formed with 79% ee (81% yield) when the reaction was catalyzed by the J ,J -DBFOX/Ph aqua nickel(II) complex at room temperature in dichloromethane. Reactions using either the anhydrous complex or the aqua complex with MS 4 A gave a racemic adduct, however, indicating that the aqua complex should be more favored than the anhydrous complex in thiol conjugate additions. Slow addition of thiophenol to the dichloromethane solution of 3-crotonoyl-2-oxazolidinone was ineffective for enantioselectivity. Enantioselectivity was dramatically lowered and reversed to -17% ee in the reaction at -78 °C. A similar tendency was observed in the reactions in diethyl ether and THF. For example, a satisfactory enantioselectivity (80% ee) was observed in the reaction in THF at room temperature, while the selectivity almost disappeared (7% ee) at 0°C. 

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