Trans-racemates

The HCI salt cis-racemate and trans-racemate of N-methyl-4-(3,4-dichlorophenyl)-l,2,3,4-tetrahydro-l-naphthalenamine hydrochloride, was dissolved in hot methanol (2 L). Upon addition of ether (1200 ml) and cooling overnight, cis-(lS)(lR)-N-methyl-4-(3,4-dichlorophenyl)-l,2,3,4-tetrahydro-l-naphthalenamine hydrochloride precipitated (47 g, melting point 290°-291°C). The supernatant was evaporated under vacuum to dryness and the residue triturated with acetone. The triturated residue (ca. 90% cis-racemate, 10% trans-racemate) was recrystallized from methanol ether (1 1) to yield another 20 g of the same product. The total yield of cis-(lS)(lR)-N-methyl-4-(3,4-dichlorophenyl)-l,2,3,4-tetrahydro-l-naphthalenamine hydrochloride was 67g, 68% yield melting point 289°-290°C. 

Addition of 3-methylcyclohex-2-enone to C6o afforded four stereoisomers comprising the diastereoisomeric cis- and trans racemates ( )-195 and ( )-196 (ratio 40 60), respectively, which were identified by 1H-NMR coupling constant analysis (Figure 1.44)238 The separation of the enantiomers of... 

Reaction of the benzodioxocine 170 with the epoxidation reagent resulted in the epoxide 171, which was then opened with sodium azide in situ to provide trans-racemic azide 172 (Scheme 18) <2004MI265>. Reduction of the azide 172 by hydrogenolysis using Pd on carbon gave trans-racemic amine 173 in 70% yield over three steps. On acylation of the amine with acetic anhydride, the trans-racemic alcohol 174 was formed, which was then oxidized with Dess-Martin periodinane into the unstable dioxocinone 175. 

Kanerva et al. resolved ethyl esters of ten alicyclic (i-aminocarboxylic acids by lipase catalysis in organic solvents. The resolutions were based on acylation of the amino group at the / -stereogenic centre with various 2,2,2-trifluoroethyl esters. From the cis and trans racemic esters 42, all four enantiomers of 2-ACPC were prepared. The absolute configurations of 43 and 44 were proved by transformation to the known 2-ACPC enantiomers by hydrolysis and subsequent desalting with an anion-exchange resin [85]. 

Substitution at C-l of the non-aromatic ring of tetralin with methyl introduces high stereoselectivity. Of the C-l-methylated 8-OH-DPAT enantiomers, only cis (2R)-3 displays high affinity for 5-HT1A receptors (Table 3). The antipode cis (2S)-4 is hardly active. The trans racemate (5,6) shows low affinity [9]. Cis (2R)-3 however is not selective for 5-HT receptors. The compound displays also affinity for dopamine D2 receptors. In functional tests cis (2R)-3 behaves as a mixed partial 5-HTjA receptor agonist/D2 receptor antagonist [22]. 

Qassical resolution of racemates by means of enantiomericaUy pure amines is an established methodology, which is also used at the industrial scale. (IH)-irans-Chrysanthemic acid may be separated out of the trans-racemate by using for instance l-(2-naphthyl)ethylamine or ephedrine. 

Isomerases Various Isomerizations, C=C bond migration, cis-trans racemizations, etc. fructose-glucose isomerase... 

Initially, Bogert proposed that this reaction always went through an alkene intermediate due to the observation that when the reaction was stopped (quenched before completion) the presence of an olefinic substrate was supported by 30-40 mol % uptake of Br2, while others have thought alkene or carbocation formation unnecessary. An alternative mechanism for some substrates has been proposed in light of experimental results. The key experiments for this alternative mechanistic view was done by Barnes and Olin, wherein they described the reaction of trans-racemic and trans-optically-enriched alcohol 24 with 90% H2SO4 to provide mainly the cis-isolated product 25 which when optically enriched 24 was used, the product 25 rotated plane-polarized light. These results suggested that an alternative mechanism without free cation formation and/or intermediate alkene formation was possible. ... 

These relationships of trans-racemic and cis-meso structures differ from those observed for ROMP products obtained with most conventional catalyst systems (described in the previous sections). For... 

SCHEME 20.15 Coordination of the previously formed double bond to Ti gives a trans-racemic dyad when anfi-7-methylnorbornene approaches the Ti=C face of E from the front side with its cyclic structure pointing down ([Ti] = Cp2Ti, P = polymer chain, arrow used to indicate monomer approach). 

Tacticity arises in these polymers from the relative orientation of the five membered rings in the polymer backbone as shown in structure (32). Thus, depending on the configuration of the adjacent double bond c/ -syndiotactic cis racemic, c ), cis isotactic cis meso, c ), trans syndiotactic trans racemic, t ) and /raw -isotactic trans meso, /m) dyads result. 

For separation of the 1-R-trans acid from trans racemate several optically active amines were successfully apphed ... 

For separation of cis/trans racemic mixtures of chrysanthemic acid into pure ds or trans racemates, the lower solubihty of ds acid [7], the faster saponification of trans ester [91], the abihty of cis acid for intramolecular reactions [92] or the pK-differences between cis and trans in connection with phase distribution [93] can be exploited. 

However, treatment of this ds/trans add with sulfuric add at 160 °C yields trans racemate [107]. On the other hand the trans ester, when treated with sulfuric acid in pentane at room temperature, gives rise to a irreversible ring opening at carbon bond C —and formation of optically active lavandulyl esters 72 [108] as seco chrysanthemates. Loss of optical activity is accomphshed by moderate thermal treatment of 1-S-configurated anhydrides 73 in the presence of iodine [110] or in the presence of a Lewis acids (Reaction scheme 44). 

The treatment of the optically active adds with aluminum bromide at room temperature [111], yielding mainly trans racemate offers still milder conditions. The boron tribromide or aluminum tribromide [109] catalyzed racemization of free 1-S-acid in the presence of hydroperoxides [108] proceeds even better. Similarly useful... 

Separation of the IRcis isomeric acid from the cis/trans racemate may be accomplished according to Ref. [73, 304]. 

Synthetic highlight Diastereoselective production of rac-menthol from its aromatic precursor is achieved by site-selective isopropylation and diastereoselective hydrogenation to the all-trans racemate. Enantioselective allylic amine-enamine-imine rearrangement of an acyclic diene-allylic amine, catalyzed by an Rh(I)-(—)-BINAP complex, affords (—)-menthol the process has been scaled-up to production of 1,000 tons/year. 

The industrial method is developed based on the preparation of ketimine TM 9.3b followed by reduction. It should be observed that ketone TM 9.3a and imine TM 9.3b are racemic compounds. By non-stereoselective reduction of imine to methylamine, diastereomeric 1,4-dr and, A-trans racemates are formed. 

ROMP of 4-methylcyclopentene leads to the formation of a polymer with four different configurations, cis-meso, cis-racemic, trans-racemic, trans-meso stereochemical, owing to the relative positioning of the methyl substituents. ... 

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