Synthesis route

The following schemes show for each of the above-mentioned, commercialized fungicides one possible synthesis route, taken from published sources, mostly patents. For chemists, this should give an impression how individual compounds can be synthesized, and can also suggest synthesis strategies and chemical reactions on which the technical processes are based. But this is not necessarily so in each case, since the production processes usually are not published. 

For synthetic organic chemists, the schemes are self-explanatory and require no detailed comment. In strobilurins, the ortho substitution pattern at the central bridging ring favors the use of easy accessible starting materials or intermediates in which a lactone-type ring is cleaved to obtain pharmacophores and side chains built up in the proper ortho connection. As already mentioned at the end of Section 13.2.3.4, the thermodynamically favored E-configuration of the differ- 

1 Philips McDougall AgriService, November 2005, Products Section -2004 Market, p. 205 and pp. 253—260. 

5 Clough, J. M., Godfrey, C. R. A., in Hutson, D. H., Miyamoto, J. (Eds.), Fungicidal Activity, Chemical and Biological Approaches to Plant Protection, John Wiley Sons, New York, 1998, pp. 109-148. 

in Copping, L. G. (Ed.), Crop Protection Agents From Nature, The Royal Society of Chemistry, Cambridge, UK, 1996, pp. 50-80. 

The copper atoms in the vast majority of the clusters can be assigned a formal charge of +1, while the chalcogen ligands are formally viewed as E or RE groups. Some of the selenium-bridged species, however - and nearly all copper telluride clusters - form nonstoichiometric compounds that display mixed valence metal centers in the formal oxidation states 0 and +I or +I and +11. These observations correlate with those made for the binary phases CU2S, Cu2 xSe, and Cu2- Te [38-40]. 

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Current research in LHASA is focused on developing new methods assisting users in choosing the most appropriate strategy for their target structures. Furthermore, the development of criteria for the evaluation of synthesis routes and/or algorithms for selecting optimal synthesis routes within the tree are discussed [34]. 

Just as a researcher will perform a literature synthesis for a compound, there are computer programs for determining a synthesis route. These programs have a number of names, among them synthesis design systems (SDS) or computer-aided organic synthesis (CAOS) or several other names. 

In principal, synthesis route prediction can be done from scratch based on molecular calculations. However, this is a very difficult task since there are so many possible side reactions and no automated method for predicting all possible products for a given set of reactants. With a large amount of work by an experienced chemist, this can be done but the difficulty involved makes it seldom justified over more traditional noncomputational methods. Ideally, known reactions should be used before attempting to develop unknown reactions. Also, the ability to suggest reasonable protective groups will make the reaction scheme more feasible. 

Creating synthesis route prediction programs has been the work of a relatively small number of research groups in the world. There are nearly as many algorithms as there are researchers in the field. However, all these can be roughly classified into three categories. 

These programs systematically determine which bonds could be broken or formed in order to obtain the desired product. This results in generating a very large number of possible synthesis paths, many of which may be impossible or impractical. Much work has been done to weed out the unwanted synthesis routes. One major strength of this technique is that it has the capacity to indicate previously unexplored reactions. 

Database searches can be used to find a reference to a known compound with a matching substructure. This is a particularly good technique if a portion of the molecule has an unusual structure. It may indicate a synthesis route or simply identify a likely starting material. 

A second scheme uses a database of known chemical reactions. This more often results in synthesis routes that will work. However, this occurs at the expense of not being able to suggest any new chemistry. This method can also give many possible synthesis routes, not all of which will give acceptable yield or be easily carried out. The quality of results will depend on the database of known reactions and the means for determining which possible routes are best. These are often retro synthetic algorithms, which start with the desired product and let the researcher choose from a list of possible precursors. 

The program is used by first building the target molecule. It then generates a list of possible precursors. The user can choose which precursor to use and then obtain a list of precursors to it. The reaction name and conditions can also be displayed. Once a satisfactory synthesis route is found, it can be printed without all the other possible precursors included. The drawing mode worked well and the documentation was well written. 

CAOS (computer aided organic synthesis) a program for predicting a synthesis route... 

Other possible chemical synthesis routes for lactic acid include base-cataly2ed degradation of sugars oxidation of propylene glycol reaction of acetaldehyde, carbon monoxide, and water at elevated temperatures and pressures hydrolysis of chloropropionic acid (prepared by chlorination of propionic acid) nitric acid oxidation of propylene etc. None of these routes has led to a technically and economically viable process (6). 

Nitroethane. The principal use of nitroethane is as a raw material for synthesis in two appHcations. It is used to manufacture a-methyl dopa, a hypertensive agent. Also, the insecticide 3 -methyl-A/-[(methylcarbamoyl)oxy]thioacetimidate [16752-77-5] can be produced by a synthesis route using nitroethane as a raw material. The first step of this process involves the reaction of the potassium salt of nitroethane, methyl mercaptan, and methanol to form methyl methylacetohydroxamate. Solvent use of nitroethane is limited but significant. Generally, it is used in a blend with 1-nitropropane. 

Nucleophilic Substitution Route. Commercial synthesis of poly(arylethersulfone)s is accompHshed almost exclusively via the nucleophilic substitution polycondensation route. This synthesis route, discovered at Union Carbide in the early 1960s (3,4), involves reaction of the bisphenol of choice with 4,4 -dichlorodiphenylsulfone in a dipolar aprotic solvent in the presence of an alkaUbase. Examples of dipolar aprotic solvents include A/-methyl-2-pyrrohdinone (NMP), dimethyl acetamide (DMAc), sulfolane, and dimethyl sulfoxide (DMSO). Examples of suitable bases are sodium hydroxide, potassium hydroxide, and potassium carbonate. In the case of polysulfone (PSE) synthesis, the reaction is a two-step process in which the dialkah metal salt of bisphenol A (1) is first formed in situ from bisphenol A [80-05-7] by reaction with the base (eg, two molar equivalents of NaOH),... 

An alternative synthesis route for PES involves the partial hydrolysis of dichlorodiphenyl sulfone (2) with base to produce 4-chloro-4 -hydroxydiphenylsulfone [7402-67-7] (3) followed by the polycondensation of this difimctional monomer in the presence of potassium hydroxide or potassium carbonate (7). 

Other Synthesis Routes. Several alternative routes to the nucleopbilic substitution synthesis of polysulfones are possible. Polyethersulfone can be synthesized by the electrophilic Eriedel-Crafts reaction of bis(4-chlorosulfonylphen5l)ether [121 -63-1] with diphenyl ether [101-84-8] (11—13). 

The single-monomer route (eq. 5) is preferred as it proves to give more linear and para-linked repeat unit stmctures than the two-monomer route. Other sulfone-based polymers can be similarly produced from sulfonyl haUdes with aromatic hydrocarbons. The key step in these polymerisations is the formation of the carbon—sulfur bond. High polymers are achievable via this synthesis route although the resulting polymers are not always completely linear. 

Cycloahphatic amine synthesis routes may be described as distinct synthetic methods, though practice often combines, or hybridi2es, the steps that occur amination of cycloalkanols, reductive amination of cycHc ketones, ring reduction of cycloalkenylarnines, nitrile addition to ahcycHc carbocations, reduction of cyanocycloalkanes to aminomethylcycloalkanes, and reduction of nitrocycloalkanes or cycHc ketoximes. 

G s-Ph se Synthesis. A gas-phase synthesis route to making fine, pure SiC having controllable properties has been described (78,79). Methane was used as a carbon source if required, and the plasma decomposition of three feedstocks, siUcon tetrachloride [10026-04-7] SiCl, dimethyl dichi orosilane, and methyltrichlorosilane [75-79-6] CH Cl Si, into fine SiC powders was investigated. 

Select a process chemistry or synthesis route that is inherently safer. 

Select a process chemistry or synthesis route that is inherently safer (e.g., nontoxic, nonflammable materials, less severe operating condition)... 

Fig. 1. The synthesis route for ORNL s porous carbon fiber-carbon binder composites.

For rayon fiber based eomposites (Seetions 3 and 4) the fiber and powdered resins were mixed in a water slurry in approximately equal parts by mass. The isotropie piteh earbon fiber eomposites (Seetion 5) were manufaetured with less binder, typically a 4 1 mass ratio of fiber to binder being utilized. The slurry was transferred to a molding tank and the water drawn through a porous sereen under vacuum. In previous studies [2] it was established that a head of water must be maintained over the mold screen in order to prevent the formation of large voids, and thus to assure uniform properties. The fabrieation proeess allows the manufaeture of slab or tubular forms. In the latter case, the cylinders were molded over a perforated tubular mandrel covered with a fine mesh or screen. Moreover, it is possible to mold eontoured plates, and tubes, to near net shape via this synthesis route. 

Hazardous chemicals or mixtures may be replaceable by safer materials. These may be less toxic per se, or less easily dispersed (e.g. less volatile or dusty). Substitution is also applicable to synthesis routes to avoid the use of toxic reactants/solvents or the production, either intentionally or accidentally, of toxic intermediates, by-products or wastes. 

Process Synthesis Route How to make the product What route What reactions, materials, starting points Research and Development chemists research Known synthesis routes and techniques... 

Chemical Flowsheet Basic unit operation selection with flow rates, conversion factors, temperatures, pressures, solvents and catalyst selection Process synthesis route Laboratory and pilot scale trials Knowledge of existing processes... 

Basic process chemistry using less hazardous materials and chemical reactions offers the greatest potential for improving inherent safety in the chemical industry. Alternate chemistry may use less hazardous raw material or intermediates, reduced inventories of hazardous materials, or less severe processing conditions. Identification of catalysts to enhance reaction selectivity or to allow desired reactions to be carried out at a lower temperature or pressure is often a key to development of inherently safer chemical synthesis routes. Some specific examples of innovations in process chemistry which result in inherently safer processes include ... 

Rogers and Hallam (1991) provide other examples of chemical approaches to inherent safety, involving synthesis routes, reagents, catalysts and solvents. 

Research chemists have many opportunities to incorporate inherent safety in the choice of chemical synthesis route, including ... 

Examples of Synthesis Routes Inherently Safer Than Others As summarized by Bodor (1995), the ethyl ester of DDT is highly effective as a pesticide and is not as toxic. The ester is hydrolytically sensitive and metabolizes to nontoxic products. The deliberate introduction of a structure into the molecule which facilitates hydrolytic deactivation of the molecule to a safer form can be a key to creating a chemical product with the desired pesticide effects but without the undesired environmental effects. This technique is being used extensively in the pharmaceutical industry. It is applicable to other chemical industries as well. 

An alternative synthesis route is described by Kleeman 8i Engel. 

During the late seventies and early eighties, when oil prices rose after the 1973 war, extensive research was done to change coal to liquid hydrocarbons. However, coal-derived hydrocarbons were more expensive than crude oils. Another way to use coal is through gasification to a fuel gas mixture of CO and H2 (medium Btu gas). This gas mixture could be used as a fuel or as a synthesis gas mixture for the production of fuels and chemicals via a Fischer Tropsch synthesis route. This process is... 

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