Demonstration Templates

The following Conformance Demonstration Template is suggested as a possible format. 

At the end of this chapter a conformance demonstration template is suggested which, when completed for a specific product or system assessment, will offer evidence of conformance to the safety integrity level (SIL) in question. 

The demonstration template tables at the end of this chapter cater for the latter case. Chapter 8, which covers the restricted subset of lEC 61511, also caters for application software. 

The following Conformance Demonstration Template is suggested as a possible format. The authors (as do many guidance documents) counsel against SIL 4 targets. In the event of such a case, more rigorous detail from the Standard would need to be addressed. 

In order to justify that the SIL requirements have been correctly selected and satisfied, it is necessary to provide a documented assessment. The following Conformance Demonstration Template (for both hardware and software) is suggested as a possible format. 

There are many ingenious and successful routes now developed for nanocry stalline syntliesis some rely on gas phase reactions followed by product dispersal into solvents [7, 9,13,14 and 15]. Otliers are adaptations of classic colloidal syntlieses [16,17,18 and 19]. Electrochemical and related template metliods can also be used to fomi nanostmctures, especially tliose witli anisotropic shapes [20, 21, 22 and 23]. Ratlier tlian outline all of tlie available metliods, this section will focus on two different techniques of nanocrystal syntliesis which together demonstrate tlie general strategies. 

Newkome and co-workers have demonstrated the operation of a template effect in the formation of a pyrido-ester-crown. In the reaction shown in Eq. (2.8), they treated 2-clTloronicotinoyl cliloride with either the disodium or dipotassium salt of pentaethylene glycol. TJie two reactions were conducted under identical conditions except for the presence of sodium vs. potassium cations. Since the product is a six-oxygen macrocycle, its formation would be expected to be favored by K" rather than Na" counter ions for the glycolate. In fact, the yields of crown-lactone were 30% and 48% respectively when Na" and K" were the templating cations. 

Because dideoxynucleotides lack 3 -OH groups, these nucleotides cannot serve as acceptors for 5 -nucleotide addition in the polymerization reaction, and thus the chain is terminated where they become incorporated. The concentrations of the four deoxynucleotides and the single dideoxynucleotide in each reaction mixture are adjusted so that the dideoxynucleotide is incorporated infrequently. Therefore, base-specific premature chain termination is only a random, occasional event, and a population of new strands of varying length is synthesized. Four reactions are run, one for each dideoxynucleotide, so that termination, although random, can occur everywhere in the sequence. In each mixture, each newly synthesized strand has a dideoxynucleotide at its 3 -end, and its presence at that position demonstrates that a base of that particular kind was specified by the template. A radioactively labeled dNTP is included in each reaction mixture to provide a tracer for the products of the polymerization process. 

The principle was demonstrated using triazine herbicides as templates and by varying the type of functional monomer and the monomer composition. With a final batch size of ca. 40 mg of monomer, the consumption of monomers and template is significantly reduced and the synthesis and evaluation can take place in standard high-performance liquid chromatography (UPLC) autosample vials. After synthesis. 

The first total synthesis of erythronolide B (1) by Corey stands as an event of great historical significance in synthetic chemistry it provides a powerful illustration of the utility of Corey s methods of macrolactonization and it demonstrates, in a particularly insightful way, the value of using readily accessible six-membered ring templates for the assembly of contiguous arrays of stereo-genic centers. 

In this beautiful synthesis of periplanone B, Still demonstrated a classical aspect and use of total synthesis - the unambiguous establishment of the structure of a natural product. More impressively, he demonstrated the usefulness of the anionic oxy-Cope rearrangement in the construction of ten-membered rings and the feasibility of exploiting conformational preferences of these medium-sized rings to direct the stereochemical course of chemical reactions on such templates. 

The authors found that the yield of 30-mer (a product with 5—6 linkages) was not much smaller than that of 10-mer or 12-mer. These facts indicate that the stability of the complex between the oligonucleotides and the complementary template is the most important factor in determining the extent of the condensation. The strong influences of template polymer (Poly C) are demonstrated in Fig. 9, in which the elution profile is shown of the polymerization products of (2 MeIp)6 in the presence of Poly C (B) and in their absence (A). 

In another paper, the same authors investigated the 1,3-dipolar cycloaddition on 2-(lH)-pyrazine scaffolds 72 and electron-rich azides, using Cu(0) and CUSO4 as pre-catalysts. To demonstrate the versatility of this approach, they reported the generation of different templates (73 in Scheme 25) as an application of cUck chemistry . They also investigated the Diels-Alder reaction of the so obtained triazoles with dimethyl acetylenedicarboxylate (DMAD), under microwave irradiation. The latter reaction allowed obtaining various pyridinones in good yields (74 and 75 in Scheme 25) [57]. 

In situ thiol oxidation can also be done just after the tetraethoxysilane hydrolysis. Both MPTMS and H2O2 are added simultaneously before aging. This was demonstrated by Stucky et al. [69] on SBA-15 containing ffS03 and additional alkyl groups, followed by Mbaraka et al. [63], and Yang et al. [70], the latter including template removal. In situ oxidation avoids residual unreacted thiols, typically observed by postsynthetic routes. 

The application of zeolite membranes in microreactors is still in an early stage of development, and suffers sometimes from unexpected problems arising from template removal [70]. However, several application examples of zeolite membranes in microstructured devices have been demonstrated yielding similar advantages as were to be expected from experiences on the macroscale. Because of the high surface to volume ratio of microreactors, the application of zeolite membranes in these systems has great potential. 

The added value, variety of use, and methods to apply zeohte coatings or films in sensor apphcations has been convincingly demonstrated. Although current trends focus on miniaturization of sensors and creating smaUer zeohte crystals and thinner films, to decrease the response time of the sensor [79], often thick-film technology is sufficient to apply zeohte films for this type of application. Some sensor materials cannot withstand the high temperatures necessary for template removal by air calcination. Recent work demonstrated that ozonication yields... 

---