Further Process Optimization

commercially available reagents 45-47 were examined. Phosphorous-based azide reagent 45 could not be used as azide source. Sulfonyl azides 46 and 47 gave more promising results with 4-phenylbut-l-ene (3), but with more stericaUy hindered substrates, yields were much lower. With these two reagents, precipitation and deactivation 

In further studies, the potential of these new azide source was then analyzed (Table 4.4). For 4-phenylbut-l-ene (3), the use of only 1.5 equivalents of azide 49 or 50 gave 

Entry Aikene Product Yield with 3 Yield with Yield d with 

At this point, we decided to reexamine the functional group tolerance of the hydroazi-dation reaction with this class of olefins, as the tertiary azides are not easily accessed via substitution reactions and no chiral center is formed during the reaction, alleviating issues of diastereoselectivity with chiral substrates (Table 4.5)  

Alkenes 33 and 35 and esters gave similar yields as with azide 53 (entries 1,2,4,5). However, for substrates where the alkene functionality is connected to an amino acid through an ester bond, slightly lower yields were observed (entries 8,9). 

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Further process optimization by Thiruvengadam and co-workers (Thimvengadam et al., 1999), led to a novel, stereoselective, scalable two-step process devoid of chromatography for chiral 2-azetidinone construction (Scheme 13.4). As above, the titanium-enolate of chiral oxazolidinone 11a was preformed, but now when reacted with well behaved imines of type 16, affords the unexpected anti-addition product. This surprising result was further supported by careful comparison to minor antiproducts obtained in the earlier aldol-addition methodology and determination that the major product was indeed 17a (undesired RSR series). Adjustment of the oxazolidinone absolute stereochemistry to the fortuitously less expensive 2S-series afforded the desired diastereo-mer 17b in 95% de and in 50-70% yield. Recrystallization improved the stereochemical purity to >99% de. 

Granulation particle size did not impact the release rate. In addition, tableting at various compression forces had no significant impact on the release rate of the tablets. This knowledge that variability in tablet manufacture resulted in a uniform sustained release dosage form provided an advantage for further process optimization and scale-up, as shown in Figure 23. 

For further process optimization, the minimum-deformation forging was selected primarily because it was capable of producing a high-quality flash-free forging with no draft angles, thus eliminating subsequent maahining steps... 

The basic R D flow sheet is a direct result of the optimization process during the feasibility study. This and the first experiments with process parameters are the basis for a laboratory-scale plant for a possible further process optimization. 

Research Trends. Research since the late 1970s appears to have centered on further process modifications and optimization of conventional processes, reduction in pollution, evaluation of potentially more efficient processing technology, increased use of less expensive softwood sources to extend the available hardwood suppHes, and accommodation of recycled newspaper pulp (see Recycling, paper). 

V-Sb-oxide based catalysts show interesting catal)dic properties in the direct synthesis of acrylonitrile from propane [1,2], a new alternative option to the commercial process starting from propylene. However, further improvement of the selectivity to acrylonitrile would strengthen interest in the process. Optimization of the behavior of Sb-V-oxide catalysts requires a thorough analysis of the relationship between structural/surface characteristics and catalytic properties. Various studies have been reported on the analysis of this relationship [3-8] and on the reaction kinetics [9,10], but little attention has been given to the study of the surface reactivity of V-Sb-oxide in the transformation of possible intermediates and on the identification of the sxirface mechanism of reaction. 

The nature of the plant material subjected to osmotic dehydration is the key point for both modeling and optimizing the osmosis in itself and as a pretreatment to further processing. The same osmotic medium, applied to different raw materials, under identical process conditions causes substantially different rates of dehydration and solute uptake. Data on these findings were reviewed previously (Lazarides et al., 1999 Torreggiani, 1995) and have been confirmed by recent research. 

Concentration> Neglecting all the nonsuspiclous values and concentrating the further analysis on the outlying data is a strategy which is sometimes very useful in process optimization, quality assurance or archeology (Figure Id). 

For process optimization problems, the sparse approach has been further developed in studies by Kumar and Lucia (1987), Lucia and Kumar (1988), and Lucia and Xu (1990). Here they formulated a large-scale approach that incorporates indefinite quasi-Newton updates and can be tailored to specific process optimization problems. In the last study they also develop a sparse quadratic programming approach based on indefinite matrix factorizations due to Bunch and Parlett (1971). Also, a trust region strategy is substituted for the line search step mentioned above. This approach was successfully applied to the optimization of several complex distillation column models with up to 200 variables. 

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