Multiple substitutions

Multiple substitution by strongly electron withdrawing groups greatly increases the acidity of phenols as the values for 2 4 dimtrophenol (4 0) and 2 4 6 trimtrophenol (0 4) m Table 24 2 attest... 

The hydrogens of benzotrifluoride can be replaced with chlorine, bromine, or iodine Although meta substitution is favored, multiple substitutions are frequently observed [J2, 33, 34, 55] (Table 8)... 

More elaborate approaches make use of multiple substitutions to generate additional information. Consider a reaction in which substitutions can be made at two sites, X and y, so that the observed response is a function of both substituents, f x,y). Expanding this in a Taylor s series gives... 

One potential problem with this procedure is that the product can sometimes act as a nitrogen nucleophile, and multiple substitutions may then occur. It is useful, therefore, to be able to distinguish the relative nucleophilicity of different amines. 

Ualike the multiple substitutions that often occur in Friedel-Crafts alkylations, acylations never occur more than once on a ring because the product acyl-benzene is less reactive than the nonacylated starting material. We ll account for this reactivity difference in the next section. 

The parent with the most substituents cited as prefixes (bridging substitution, e.g. 2,3-O-methylene, is regarded as multiple substitution for this purpose). 

It will be convenient to consider under one heading all those unsaturated systems which do not fall under any of the sections previously discussed. There are four categories which are included in this catch-all heading. They are pyridones, quinones, multiple substitution at nonequivalent sites, allenes and cumulenes, and conjugated dienes and polyenes. 

Two sets of data involving multiple substitution at nonequivalent sites have been examined. The sets studied are reported in Table XLV (sets 45-51, 45-52). Results of the correlations are set forth in Table XLVI. Significant correlations were obtained for both sets of data. 

A second mechanism of resistance involves alterations in PBPs which affect binding of /3-lactams. These changes have been found to occur by multiple substitutions through recombination rather than point mutations. Acquired penicillin resistance in Strep, pneumoniae is because of such gene mosaics which code for an altered yet functional PBP with reduced affinity for penicillin. Sections of the susceptible PBP gene have been replaced by other DNA sequences, presumably via transformation. 

The second of the resonance structures is the source of the radical reactivity displayed during oxidation and the Mn(III) in this structure must be low-spin to preserve multiplicity. Substitution at the meso-position could provide steric hindrance to analogous decompositions and reactions of the Mn(IV) complexes of ethyl- and benzylmalonic acids, and a conventional one-equivalent oxidation step becomes dominant. 

There are innumerable industrially significant reactions that involve the formation of a stable intermediate product that is capable of subsequent reaction to form yet another stable product. These include condensation polymerization reactions, partial oxidation reactions, and reactions in which it is possible to effect multiple substitutions of a particular functional group on the parent species. If an intermediate is the desired product, commercial reactors should be designed to optimize the production of this species. This section is devoted to a discussion of this and related topics for reaction systems in which the reactions may be considered as sequential or consecutive in character. 

Multiple substitution reactions are commonly encountered in industrial practice. They may be represented in general form as ... 

We are now prepared to develop quantitative relations for series-parallel reactions of the multiple substitution type considered above. 

Illustration 9.4 indicates how the concepts we have developed may be used in attempting to develop a rational reactor design for carrying out multiple substitution reactions. 

Good yields of the desired product can be obtained only when k1 > k2. Among the industrially significant reactions of this type are those involving partial oxidation and multiple substitution. Reactions represented by equation 12.3.136 were discussed in detail in Section 9.2, and that material is also pertinent here. 

At first the reactions of monochlorosilanes and siloxanes with lithium trimethylsilanolate, lithium phenyldimethylsilanolate, and lithium isopropylate were followed by gaschromatography, H NMR spectroscopy, and by nephelometric measurements [3,4]. Di- and trichlorosilanes and -siloxanes were then investigated in order to study the influence of strongly electron attracting substituents at the reaction centre [5], To prevent multiple substitution lithium ferr-butylate was used as the nucleophile for these compounds. All reactions gave high yields of products and no by-products were formed. 

Klemperer10 and Gilbert and Shapiro11 follow a similar line. The application of the concept of scope patents in the biotechnology sector is studied by Lemer.12 According to his estimate, broad patents are more valuable when there are multiple substitutes, which confirms theoretical findings. 

The nitrogen complex had already been synthesized in a solid matrix, but its decomposition kinetics and its further photolysis could be studied only in solution. The liquid noble gas technique is superior to the solid matrix technique, especially for the synthesis of multiple substituted chromium carbonyl nitrogen complexes. Their IR spectra were extremely complex in matrices, due to "site splittings" which arise when different molecules are trapped in different matrix environments /18/. 

Multiple substitutions almost always occur in the halogenation of alkanes. 

Substituents modulate the electron-donor or acceptor strengths depending upon their electron-releasing or electron-withdrawing properties as evaluated by the Hammett a+ (or a) constant(s).62 For example, the multiple substitution of methyl groups on ethylene leads to the strong re-donor 2,3-dimethyl-2-... 

From the approach suggested in J. S. Chickos, D. G. Hesse and J. F. Liebman, 7. Org. Chem., 55, 3833 (1990), we conclude that the errors of ignoring multiple substitution and a small multiple of RT will not ameliorate file seemingly disparate enthalpies of formation of file three triamines of interest. 

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