Scope and limitations of a reaction

To assess the preparative utility of an organic reaction, a knowledge of its scope 

It is impossible to evaluate all possible combinations of substrates, reagents, and solvents by experiments. It is quite cumbersome, even to run a complete factorial design with selected substrates, reagents and solvents, as was described in the examples above. To achieve a more manageable number of test systems, it is possible to use the principles of fractional factorial designs to select test systems by their principal properties To illustrate this, we shall once more make use of the Willgerodt-Kindler reaction. 

Let us pretend that the Willgerodt-Kindler reaction with acetophenone has been recently discovered. Let us also assume also that it has been shown that it can be applied also to substituted acetophenones, provided that they do not carry strong withdrawing substituents on the aromatic ring. 

To assess the general scope of the reaction it would therefore be necessary to consider the structure of the substrate, the structure of the amine, and the nature of the solvent. 

If it is assumed that the structure of the substrates can be described by the nature of the substituents, it would be possible to use common substituent parameters as descriptors of the substrates. Several studies on substituent parameters by principal components analyses have now been published.[ll] When the experiment described here were carried out, one such study was available.[lla] This study described the variation of the properties of aromatic substituents by a two-component model, and this model was used for the selection of the substrates in the present study. The principal properties of amines and solvents are also described by two-component models. Each axis in the reaction space is therfore two-dimensional, and the whole reaction space is six-dimensional. To span the whole reaction space by selecting test systems from each comer would require 2 = 64 different test systems. It would be 

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In a situation where we wish to select a series of test compounds, e.g. for determining the scope and limitations of a reaction, we are facing a problem which involves a discrete variation between the test objects. To cover the possible variation of interest in order to determine as broad a scope as possible, we have to consider all relevant properties of the reaction system. Due to possible interaction effects, all these properties must be taken into account simultaneously. This is not a trivial... 

It is often necessary to survey the scope and limitations of a reaction, a synthetic method, a reagent, or a technique to determine whether it may be applied to solving a specific problem. To facilitate access to this information, a number of reference works are available that contain reviews of reactions, reagents, techniques, and methods in organic chemistry these are often serial in nature. 

As stated previously, these activities are only part of the job of the process chemist As described in Section 2 of each chapter, titled Chemistry Development , the author(s) will focus on the advancement of synthetic organic chemistry discovered during the process development. In order to satisfy the Process Chemist s scientific curiosity and to advance synthetic organic chemistry, further optimization followed by investigation of the scope and limitations of these reactions is explored. In order to ensure the robustness of the reaction and to optimize it in a more scientific way, elucidation of the reaction mechanism is undertaken. Mechanistic studies are very beneficial in improving our synthetic organic chemistry skills and provide opportunities to raise these reactions to a further dimension, again that of Art . 

The problem of defining the scope and limitations of a photochemical reaction is more difficult than with reactions of molecules in the ground state. As we have seen, with the excited state the question as to whether the desired product will be obtained depends upon the relative rates of several possible side reactions and/or deactivation pathways. Many of these competing reactions are inherent to the excited state and, as yet, little is known about controlling them. 

Study of the scope and limitations of the reaction revealed that a broad variety of aldimine is tolerated [83]. These reactions were conducted with a loading of orga-... 

Hydrogenation of dienes with up to 20 1.0 diastereoselectivity and 99% ee is mediated by carbene complexes. The scope and limitations of these reactions were investigated.288 Asymmetric transfer hydrogenation to prochiral ketones, catalysed by a Ru(II) complex (10) or its dimer, with formic acid-triethylamine has been reported, (0 The protocol leads to high yields and enantioselectivity up to 96%. It has been suggested that 16-electron Ru(II) and the Ru-H intermediates are involved in this reaction.289... 

The present overview deals with the application of Fischer chromium carbene complexes in the benzannulation reaction for the preparation of highly substituted aromatic compounds. Before focussing on specific arenes (Section 8.5), details of the mechanism are given (Section 8.2), and the scope and limitations of the reaction are defined (Section 8.3). A short description of the experimental procedure is given thereafter (Section 8.4). Finally, the contribution deals with the application of the chromium carbene benzannulation to natural compounds and molecules with biological activity (Section 8.6). 

Is it possible to apply the method to a variety of similar substrates What are the scope and limitations of the reaction in this respect ... 

The amination of heterocyclic bases such as pyridine, quinoline, and their derivatives by alkali amides furnishes a good method for obtaining the 2-amino compounds (50-100%). The scope and limitations of the reaction have been reviewed the procedure is illustrated by the preparation of 2-aminopyridine (76%). ... 

The conversion of an acid to an amine of one less carbon may be conveniently accomplished by way of the azide and rearrangement to the isocyanate. The azide may be obtained either from the acyl chloride and sodium azide or from an ester by treatment with hydrazine and subsequent diazotization. An excellent review including scope and limitations of the reactions, selection of experimental conditions and procedures, and a tabulation of compounds prepared thereby has been presented. ... 

Specific examples have been chosen for each method, including reaction conditions and yields wherever possible. These are meant to reflect the synthetic utility of the transformation regarded in a representative sense however, even when scope and limitations of these reactions are known they can not usually be discussed in much detail. 

Summary A silicon-based technique of using RFSi(CH3)3 reagents is quite useful for introducing fluorinated substituents into perfluoroolefins and perfluoroimines, especially for constructing the highly branched derivatives of perfluoroolefins and perfluoroimines, which are otherwise difficult to synthesize. The scope and limitations of these reactions are described, and comparison of the reactivities of the perfluoroolefin and the perfluoroimine with RFSi(CH3)3 are made. 

A note of caution none of these tables were created with the intent to be comprehensive, since that would be beyond the scope of this book. The reader should always check the details for each reaction to find out the true scope and limitations of a given transformation. We welcome any suggestions on how to make this section more effective in future editions. 

The transform to be reworked was announced in advance, with literature references to the reaction being covered. A person familiar with ALCHEM (a "coder") gave a step by step walkthrough of a transform. The chemical and structural meaning of each statement was explained, triggering a wider discussion of the scope and limitations of the reaction. As new aspects of... 

If we limit the study in a first run to include only para substituted acetophenones, a series of eight systems as defined by the design in Fig 16.8 would be sufficient to afford a first check of the scope and limitations of the reaction. This would correspond to the systems summarized in Table 16.6. These systems were tested experunentally.[12]... 

With Comprehensive Asymmetric Catalysis we hope to fill this gap. Comprehensive means that all important classes of enantioselective catalytic transformations are covered but it does not imply an extensive lexicographic compilation of examples. The aim was a concise and readable overview of the field, providing a clear picture of the state of the art. The reader should be able to recognize the scope and limitations of a specific catalyst or method and find the pertinent references for a more detailed bibliographic study. The electronic version with reaction and substructure search options should be particularly useful for this purpose. 

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