Key intermediates

Once a network has been constructed it can be reviewed to determine whether the completion date and intermediate key dates are acceptable. If not, activity duration reductions have to be sought, for example, by increasing manpower or changing suppliers. 

Figure 3. Scheme of the photochemical behavior of M(CO)5 in a mixed NJAr matrix via a trigonal bipyramidal intermediate. Key O, the matrix cage and, 1E excited state of Cr(CO)5. (Reproduced from Ref. 25. Copyright 1978, American... 

Manufacturing standard—cGMP, intermediates, key intermediates, and active pharmaceutical ingredients (APIs). 

According to the ICH guidance document, introducing an intermediate (key or final) or API that does not conform to standards or specifications back into the process by repeating a crystallization step or other physical manipulation (i.e., distillation, filtration, chromatography, milling, and drying) that is part of the... 

In many separations, components are present whose relative volatilities are intermediate betwsen the light key and the heavy key. These components are termed intermediate keys or distributed keys. Intermediate keys are split between the top and bottom products. 

The d/b plot provides a useful estimate of the distribution of nonkeys and intermediate keys in tbe products. Hengstebeck (14) and Geddes... 

Stupin and Lockhart (27) also noted that as reflux is lowered from total to minimum, the separation of nonkeys first worsens (curve 2, Fig, 2,21), then improves (curve 3, Fig. 2,21), The intermediate keys follow the converse pattern, At a reflux ratio of about 1,2 to 1,5 times the minimum, component distribution resembles that of the total reflux component distribution. Detailed discussion is elsewhere (7,27). Figure 2,16 demonstrates that light nonkey6 are fractionated out in the stripping section and heavy nonkeys in the rectifying section. The d/b plot depicts this behavior (Sec. 2,4,2). 

The recent studies of 1,2-dioxetane chemiluminescence, ECL, and CIEEL have brought significant advances to the field of chemiluminescence. The relatively simple nature of these processes has allowed attention to be focused on the nature of chemiexcitation and much has been learned. In addition, these relatively simple systems subsequently have been proposed as key intermediates, key steps or key sequences in many more complicated chemi- and bioluminescent systems. 

Hydroxysuccinic acid) (Anacardiaceae), Hibiscus sabdarffa cycle intermediate key... 

Slow production of the intermediate key species (c) fast production of the key species (d) reaction in the adsorbed phase. 

Kister says that d/b plots are primarily used when there is a tight spec, on a nonkey component or a concern about the distribution of an intermediate key component. His book shows d/b curves for various feed stage locations on a plot of the mole ratio of a reference component in the distillate to the bottom product, versus the relative volatility of each component to this reference component. This plot is made on log-log paper. The optimum feed produced a curve closest to linear. The d/b plot is suggested as a troubleshooting tool in the subsection of the Troubleshooting section, Fractionation Operating Problems. ... 

Figure 21 Putative catalytic mechanism for lysidine formation by TilS. Note A. aeolicus TilS numbering. This two-step reaction is proposed to be ATP-dependent and generate an adenylated intermediate. Key residues thought to be involved in catalysis and substrate recognition are indicated. This mechanism was proposed by Nakanishi etal. Reproduced from K. Nakanishi S. Fukai Y. Ikeuchi A. Soma Y. Sekine T. Suzuki O. Nureki, Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 7487.

Intermediate key components can also fool a temperature controller. These tend to build up in close to the feed, often in the neighborhood of the preferred temperature control location, and their accumulation rate and location are seldom predictable. Techniques for preventing intermediate component accumulation are discussed in Sec. 13.7. 

Severe interference of nonkeys or intermediate keys may entirely preclude satisfactory temperature control without composition compensation. An excellent example has been described by Anderson and McMillan (13). Their column (Fig. 18.7) sepeirated water and heavy ether from a mixed alcohol stream, the top product consisting of a volatile water-ether azeotrope and a volatile ether-alcohol azeotrope. Wa-... 

Next the effects of relative volatilities on the optimal trajectory are examined. Fig. 2B shows that, for fixed reactor outlet temperature, changes in the relative volatility of intermediate key (B) from aB=1.5 to aB=3 do not produce significant difference. Because a larger ae results in a lesser separation cost and, therefore, the trajectory converges to center line at a lower conversion, but not by much. 

It must also be indicated that the presence of water in the reaction gas mixture is essential to obtain high acrylic acid yields over these mixed-metal oxide catalysts. An IR spectra of propylene on these catalysts suggest that jt-allyl intermediate (key for the acrylic acid formation) is not formed in the absence of water, while it is clearly observed when both propylene and water are present ... 

The same principle of CIEEL/ECT mechanism has also been adapted for a mechanism - (Scheme 136.5) involving dioxirane as an intermediate. Key aspects of this dioxirane mechanism are similar to the CIEEL/ECT mechanism mentioned above. The exited emitter formation involves the same annihilation of radicals (Step C4). The same 4a-hydroxyFMNH radical cation proposed earHer in the CIEEL/ECT mechanism is again formulated as a key intermediate. Hence, the correlation of flavin redox potentials with the luciferase Hght decay rates also supports this dioxirane version of the CIEEL/ECT mechanism. One difference between the two mechanisms shown in Schemes 136.4 and 136.5 is that a dioxirane species is depicted as an intermediate in the latter. As a test, dimethyldioxirane was reacted... 

The TAC is used to obtain the optimal design. For the design specifications in the second column, we set the light product to 98.5 mol% B in the distillate and the heavy product (intermediate key) to 98 mol% C in the bottoms. In the reactive distillation column, the conversion of A is set to 98% and the composition of the column overhead is 49.75 mol% B and 49.75 mol% C. Because this is a sequential configuration with the two columns not coupled together, design steps can be carried out separately. 

By setting the product specifications at 98%, light key product in the top, and intermediate key product in the bottoms, the reflux ratio and the boilup rate are manipulated to control product purities. Distillate and bottoms flows are manipulated to control the inventory of reflux-drum and column base. 

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