Synthesis route prediction

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. 

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

Two synthetic routes predicted by LHASA for the synthesis of quinoline (24) are shown in Scheme 7. LHASA S first synthetic route was the condensation of... 

Two synthetic routes predicted by LHASA for the synthesis of quinoline (24) are shown in Scheme 7. LHASA S first synthetic route was to have 2-amino-benzaldehyde (25) condense with acetaldehyde (26) to yield quinoline and water, which is essentially equivalent to the known synthesis of quinoline from the reaction of aniline with acetaldehyde and formaldehyde (77). When this transform was removed from consideration, LIMS A suggested nucleophilic addition of aniline (27) to acrolein (28) to yield quinoline and water, which is identical to a known synthesis of quinoline (75). 

Given the cost and complexity of a commercial synthesis procedure, even when identified, an unknown synthesis route requires considerable investment. For this reason computer modeling procedures have been introduced that attempt to predict new structures and examine phase transitions connecting them. Such procedures are continuously being applied [4] and, bearing in mind that fundamentals of the modeling procedures are also being debated, indications in the last few years have shown that reliable calculations of material properties can be... 

We evaluate all the possible advantages and disadvantages of each path and in so doing determine the most efficient route for synthesis. The prediction of which route is most feasible is usually based on specific restrictions or limitations of reactions in the sequence, the... 

In order to correctly approach this research it is necessary to focus (i) the chemical processes which occur during the preparation of a material and that influence their composition (synthesis route, nature of the precursor compounds, processing conditions) (ii) the necessary conditions to produce homogeneous or controlled heterogeneous materials with predictable and reproducible functional properties. 

This work has focused on the use of optimization techniques within a molecular design application to derive novel catalyst structures. The use of connectivity indices to relate internal molecular structure to physical properties of interest provides an efficient way to both estimate property values and recover a complete description of the new molecule after an optimization problem is solved. The optimization problem has been formulated as an MINLP, and the fact that the problem has been formulated in a manner which is not computationally expensive to solve (using Tabu search) gives rise to the possibility that the synthesis route for such a molecule could be derived and evaluated along with the physical properties of that molecule. Further work will include such synthesis analysis, as well as the inclusion of a much larger set of physical properties and basic groups from which to build molecules, and will work toward the design of mixtures and the prediction of mixture properties via connectivity indices. 

We evaluate all the possible advantages and disadvantages of each path and in so doing determine the most efficient route for synthesis. The prediction of which route is most feasible is usually based on specific restrictions or limitations of reactions in the sequence, the availability of materials, or other factors. We shall see an example of this in Section 7.16C. In actuality more than one route may work well. In other cases it may be necessary to try several approaches in the laboratory in order to find the most efficient or successful route. 

The first methacrylic esters were prepared by dehydration of hydroxyisobutyric esters, prohibitively expensive starting points for commercial synthesis. In 1932 J. W. C. Crawford discovered a new route to the monomer using cheap and readily available chemicals—acetone, hydrocyanic acid, methanol and sulphuric acid— and it is his process which has been used, with minor modifications, throughout the world. Sheet poly(methyl methacrylate) became prominent during World War II for aircraft glazing, a use predicted by Hill in his early patents, and since then has found other applications in many fields. 

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