Isomers, separation using

Figure 5. Optical isomer separation using optically active metal chelate mobile...

Gamble, T. N., C. Ramachandran, and K. P. Bateman, Phosphopeptide isomer separation using capillary zone electrophoresis for the study of protein kinases and phosphatases. Anal. Chem., 71, 3469-3476, 1999. 

If thawing is necessary, never heat the TDI above 43°C (110 F). Prolonged overheating will cause dimer formation (see Heat above). After thawing, mix the TDI to eliminate isomer separation. Use a tank agitator or a circulating pump. 

In contrast to trace impurity removal, the use of adsorption for bulk separation in the liquid phase on a commercial scale is a relatively recent development. The first commercial operation occurred in 1964 with the advent of the UOP Molex process for recovery of high purity / -paraffins (6—8). Since that time, bulk adsorptive separation of liquids has been used to solve a broad range of problems, including individual isomer separations and class separations. The commercial availability of synthetic molecular sieves and ion-exchange resins and the development of novel process concepts have been the two significant factors in the success of these processes. This article is devoted mainly to the theory and operation of these Hquid-phase bulk adsorptive separation processes. 

Isomer separation beyond physical fractional crystallization has been accompHshed by derivatization using methyl formate to make /V-formyl derivatives and acetic anhydride to prepare the corresponding acetamides (1). Alkaline hydrolysis regenerates the analytically pure amine configurational isomers. 

The polyamide copolymer of dodecanoic acid with methylenedi(cyclohexylamine) (MDCHA, PACM) was sold as continuous filament yam fiber under the tradename QIANA. As late as 1981, over 145,000 t was produced using high percentages, typically 80%, of trans, trans MDCHA isomer. The low melting raffinate coproduct left after t,t isomer separation by fractional crystallisation was phosgenated to produce a Hquid aUphatic diisocyanate marketed by Du Pont as Hylene W. Upon terrnination of their QIANA commitment, Du Pont sold the urethane intermediate product rights to Mobay, who now markets the 20% trans, trans—50% cis, trans—30% cis, cis diisocyanate isomer mixture as Desmodur W. In addition to its use in polyamides and as an isocyanate precursor, methylenedi (cyclohexyl amine) is used directiy as an epoxy curative. The Hquid diamine mixture identified historically as PACM-20 is marketed as AMICURE PACM by Anchor Chemical for performance epoxies. 

Ethyltoluene is manufactured by aluminum chloride-cataly2ed alkylation similar to that used for ethylbenzene production. All three isomers are formed. A typical analysis of the reactor effluent is shown in Table 9. After the unconverted toluene and light by-products are removed, the mixture of ethyltoluene isomers and polyethyltoluenes is fractionated to recover the meta and para isomers (bp 161.3 and 162.0°C, respectively) as the overhead product, which typically contains 0.2% or less ortho isomer (bp 165.1°C). This isomer separation is difficult but essential because (9-ethyltoluene undergoes ring closure to form indan and indene in the subsequent dehydrogenation process. These compounds are even more difficult to remove from vinyltoluene, and their presence in the monomer results in inferior polymers. The o-ethyltoluene and polyethyltoluenes are recovered and recycled to the reactor for isomerization and transalkylation to produce more ethyltoluenes. Fina uses a zeoHte-catalyzed vapor-phase alkylation process to produce ethyltoluenes. 

Only trace amounts of side-chain chlorinated products are formed with suitably active catalysts. It is usually desirable to remove reactive chlorides prior to fractionation in order to niinimi2e the risk of equipment corrosion. The separation of o- and -chlorotoluenes by fractionation requires a high efficiency, isomer-separation column. The small amount of y -chlorotoluene formed in the chlorination cannot be separated by fractionation and remains in the -isomer fraction. The toluene feed should be essentially free of paraffinic impurities that may produce high boiling residues that foul heat-transfer surfaces. Trace water contamination has no effect on product composition. Steel can be used as constmction material for catalyst systems containing iron. However, glass-lined equipment is usually preferred and must be used with other catalyst systems. 

Column crystalhzers of the end-fed type can be used for purification of many eutectic-type systems and for aqueous as well as organic systems (McKay loc. cit.). Column ciystaUizers have been used for xylene isomer separation, but recently other separation technologies including more efficient melt ciystaUization equipment have tended to supplant the Phillips style ciystaUizer. 

The cresols occur in cresylic acid, a mixture of the three cresols together with some xylenols and neutral oils, obtained from coal tar distillates. Only the /n-cresol has the three reactive positions necessary to give cross-linked resins and so this is normally the desired material. The o-isomer is easily removed by distillation but separation of the close-boiling m- and p-isomers is difficult and so mixtures of these two isomers are used in practice. 

Although many attempts have been made to separate or exclusively synthesize one isomer of an unsymmetrically substituted phthalocyanine,72-89-296,297 the product mixture has been separated in only two cases.96 103,104 Besides the chromatographic separation of the statistical product mixture it is also possible to prepare exclusively the D4h isomer by use of steric hindrance of bulky substituents, e.g. 7-ferr-butylnaphthalene-l,2-dicarbonitrile only forms the respective An isomer of the tetra(to -butyl)-substituted 1,2-NcFe by heating in hexan-l-ol.73 Recently, some 1,8,1 5,22-substituted pure isomers have also been synthesized by the use of bulky substituents in 3-substituted phthalonitriles298,299 at low temperature (see Section 2.1.4.).94... 

However, the products are separated using ion-exchange columns and the starting material is a derivative rattier than a precursor of the racemic amino add, thus making the total process drcuitous since it involves several chemical steps in addition to die enzymatic resolution step. Furthermore, racemisation of the unwanted isomer is not easily accomplished. 

These GC conditions are suitable for analyzing many prostaglandins, thromboxanes, leuko-trienes, and other metabolites of arachidonic acid, such as the hydroxyeicosatetraenoic (HETE) acids. However, the 5-, 12-, and 15-HETE isomers are difficult to separate using GC methods. Sometimes the methyl ester-TMS derivatives provide a better GC separation, or for ketoprostaglandins, the MO-methyl ester-TMS derivatives often give a better separation... 

They avoided the obvious Friedel-Crafts synthesis of (33), presumably to avoid the separation of o and p isomers, and used instead either Grignard route to (34),... 

In the recent past separation of isomers has been attempted using aqueous liquid membranes based on p-cyclodextrin. Thus, separation of a mixture of o- and p-nitroaniline (in 80% i-octanol, 20% -heptane) has been studied, with the p-isomer showing a selectivity of 5 at 0.7 molar p-cyclodextrin. Even stereoisomers of stilbene cis and trans) were separated using a 0.02 to 0.2 M cyclodextrin solution, but the selectivity was less than 2 (Mandal et al, 1998). 

Using these equations, the KI values for four known pheromone components are estimated to be 1807.7 for Me2,Me5-17 H, 1790.6 for Me5,Me9-17 H, 1788.6 for Me5,Mell-17 H, and 1783.5 for Me7, Mell-17 H. These positional isomers separately elute from a capillary GC column in a coincidental order with these KI values [105,106],indicating the usefulness of IEX(opt) for the pheromone research. 

IsoSiv [Isomer separation by molecular sieves] A process for separating linear hydrocarbons from naphtha and kerosene petroleum fractions. It operates in the vapor phase and uses a modified 5A zeolite molecular sieve, which selectively adsorbs linear hydrocarbons, excluding branched ones. Developed by Union Carbide Corporation and widely licensed, now by UOP. The first plant was operated in Texas in 1961. By 1990, more than 30 units had been licensed worldwide. See also Total Isomerization. 

Commercial LASs are complex mixtures of four individual LASs (C10-C13) with 20 possible positional isomers. Isomeric separation can be achieved by solvophobic association with SDS or host-guest interaction with cyclodextrins. Complete resolution of 19 isomers was achieved using 10 mM phosphate buffer (pH 6.8) containing 40 mM SDS and 30% acetonitrile [4]. LAS isomers in technical products were separated using a-cyclodextrin, but complete resolution of all isomers was not achieved [5]. 

Particular examples for the separation of optical isomers in the (pharmaceutical) industry include prazinquatel [51], 3-blockers [52], chiral epoxide [6],thia-diazin EMD5398 [18] and hetrazipine [7]. The Belgian company UCB Pharma uses a large-scale SMB from NOVASEP to perform optical isomer separation at a scale of several tons per year. Almost all of these separations are performed on cellulose-based stationary phases using organic eluents [4]. 

Although TMCD is not commercially available, technology for its preparation from isobutyric acid or isobutyric anhydride has been reported [79-83], A process for separation of the individual cis- and trans-isomers of TMCD has also been reported [84], TMCD is usually prepared with an approximate 50/50 cis/trans ratio, and this is the usual equilibrium isomer ratio used for polyester preparation, although polyesters prepared from other isomer ratios and from the pure m-isomer have been reported [77, 78],... 

The SMB process was invented by Broughton in 1961 and developed by Universal Oil Products under the general name Sorbex . Initially used for separating n-paraffins in bulk, it is now used for a variety of individual-isomer separations and class separations, and is currently attracting considerable interest for separating pharmaceutical enantiomers. The SMB process is described in Section 17.9.4 and in a growing literaturel-21 22>11 - 74),... 

Desorbent features are illustrated in Table 6.8 using Cg-aromatic adsorbates with BaX and KY adsorbents. The results in Table 6.8 further emphasize the desorbent characteristic requirement mentioned above. For instance, phenyldecane is a suitable desorbent for PX separation using BaX adsorbent. However, phenyldecane is too weak to desorb PX from KY adsorbents. In contrast, diphenylmethane offers good separation of PX with KY adsorbent but not with BaX. With BaX adsorbent, PX is separated from other Cg-aromatics using 1,4-diisopropylbenzene but not with other isomers of diisopropylbenzene, such as 1,3-diisopropylbenzene. 

This procedure illustrates a general method for converting substituted pyrylium salts to nitrobenzene derivatives. The reaction has been the subject of several reviews. - The yields are generally high, and under these conditions only a single product is formed, in contrast to the nitration of 1,3,5-triphenyl-benzene. The preparation of 2,4,6-triphenylnitrobenzene from the corresponding pyrylium salt eliminates isomer separation problems, which are encountered when the direct nitration procedure is used. Also, labeled compounds can readily be prepared by this method. ... 

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