Meta substitution

Another issue of regioselectivity arises with meta-substituted arylhydrazones from which either 4- or 6-substitutcd indoles can be formed. Robinson has tabulated extensive data on this point[9]. A study comparing regioselectivity of cyclization as catalysed by HCl/EtOH and ZnClj was carried out for several m-substituted arylhydrazones of diethyl ketone[10]. The results given in Table 7.1 show some dependence on catalyst but mixtures are obtained under all conditions studied. 

Introduction of nonmesogenic units in polymer chains. (E.g., using meta-substituted aromatic monomers such as isophthalic acid or resorcinol). This results in the formation of kinks in polymer chain, which disrupt lateral interactions. 

That same year saw the synthesis by Staab and Neimhoeffer of the first meta-substituted PAM. Stephens-Castro coupfing of m-iodoethynylbenzene produced the cychc hexamer 8, albeit in 4.6 % isolated yield [ 14]. Nevertheless, isolation of 8 proved conclusively that construction of larger and more complex macrocycfic structures was an attainable goal. 

Appetite Depressants. Fenduramine hydrochloride [404-82-0] is an anorexiant based on a meta-substituted ben2o triduo ride. 

Brown has proposed that the importance of meta substitution in the alkylation is related to the activity of the attacking species, and he utilized the relative reactivity of toluene and benzene in the reaction under consideration as a measure of this activity.It might be possible that the amounts of 3-isomer formed may similarly be related to the relative reactivity of thiophene and benzene in different reactions. 

Comparable stabilization of the intermediate leading to meta substitution is not possible Thus resonance involving halogen lone pairs causes electrophilic attack to be favored 

The three resonance fonns of the intennediate leading to meta substitution are all secondary carbocations. 

Band 14,13 00y.(769cm. ). Out-of-plane C—H deformation vibration. Meta substitution (Table VI). 

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) 

Benzene Nucleus Reactions. Ring substitutions, such as sulfonation and nitration, can be effected without destmction of the carbonyl group. Under the influence of the carbonyl group, meta substitution usually occurs. 

In DMSO as solvent and in the presence of nitrobenzene, aryl-de-diazoniation of the unsubstituted benzenediazonium ion leads mainly via meta substitution to 3-nitrobiphenyl, whereas in the case of the 4-nitrobenzenediazonium ion the formation of o- and -substituted products (2,4 -and 4,4 -dinitrobiphenyl) prevails (Gloor et al., 1972). 

Conversely an electron withdrawing substituent destabilizes the cyclo hexadienyl cations corresponding to ortho and para attack more than meta Thus meta substitution predominates 

This reaction cannot be elementary. We can hardly expect three nitric acid molecules to react at all three toluene sites (these are the ortho and para sites meta substitution is not favored) in a glorious, four-body collision. Thus, the fourth-order rate expression 01 = kab is implausible. Instead, the mechanism of the TNT reaction involves at least seven steps (two reactions leading to ortho- or /mra-nitrotoluene, three reactions leading to 2,4- or 2,6-dinitrotoluene, and two reactions leading to 2,4,6-trinitrotoluene). Each step would require only a two-body collision, could be elementary, and could be governed by a second-order rate equation. Chapter 2 shows how the component balance equations can be solved for multiple reactions so that an assumed mechanism can be tested experimentally. For the toluene nitration, even the set of seven series and parallel reactions may not constitute an adequate mechanism since an experimental study found the reaction to be 1.3 order in toluene and 1.2 order in nitric acid for an overall order of 2.5 rather than the expected value of 2. 

For the deracemization of phenylethanol derivatives using G. candidum under aerobic conditions (Figure 8.41b), the (S)-specific enzyme was reversible and (R) enzyme was irreversible, so (R)-alcohol accumulated when the cell and racemic alcohols were mixed [31b,c]. Para-substituted phenylethanol derivatives gave better results than meta-substituted derivatives. Sphingomonas was used for 

Hammen equation A correlation between the structure and reactivity in the side chain derivatives of aromatic compounds. Its derivation follows from many comparisons between rate constants for various reactions and the equilibrium constants for other reactions, or other functions of molecules which can be measured (e g. the i.r. carbonyl group stretching frequency). For example the dissociation constants of a series of para substituted (O2N —, MeO —, Cl —, etc.) benzoic acids correlate with the rate constant k for the alkaline hydrolysis of para substituted benzyl chlorides. If log Kq is plotted against log k, the data fall on a straight line. Similar results are obtained for meta substituted derivatives but not for orthosubstituted derivatives. 

In summary, then, the orientation of electrophilic thallation can be controlled by an appropriate manipulation of reaction conditions. Under conditions of kinetic control, ortho substitution results when chelation of the electrophilic reagent (TTFA in the studies described above) with the directing substituent permits intramolecular delivery of the electrophile, and para substitution results when such capabilities are absent this latter result is an expression of the very large steric requirements of the bulky thallium electrophile. Under conditions of thermodynamic control, however, meta substitution is observed. 

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