Benzene halogen substituents

Since various substituents are tolerated, the Friedlander reaction is of preparative value for the synthesis of a large variety of quinoline derivatives. The benzene ring may bear for example alkyl, alkoxy, nitro or halogen substituents. Substituents R, R and R" also are variable. The reaction can be carried out with various carbonyl compounds, that contain an enolizable a-methylene group. The reactivity of that group is an important factor for a successful reaction. 

The equilibrium concentrations of many disubstituted benzenes (containing alkyl and halogen substituents) show that the meta isomer is in nearly all cases the most thermodynamically stable. It is not obvious why this should be so. Shine182 had discussed this problem in terms of the relative sizes of the standard enthalpy and entropy changes between any pair of isomers. 

In the case of mono-olefins halogen substituents again reduce the basicity, as in the case of benzene. Unfortunately no information is available which would permit a comment as to whether the halogen atom causes this effect only if it is directly linked to the C=C double bond or whether an effect is also still exerted by an adjacent saturated halogen-substituted C-atom. With multiple halogen substitution the basicity falls even more as may be seen from the examples of chlorine-substituted ethylenes in Table 17. 

Halogen substituents withdraw electron density from the aromatic nucleus but direct olp-through resonance effects. The result is that halobenzenes undergo nitration with more difficulty relative to benzene. The nitration of chlorobenzene with strong mixed acid gives a mixture of 2,4- and 2,6-isomeric dinitrochlorobenzenes in which the former predominates." The nitration of 2,4-dinitrochlorobenzene to 2,4,6-trinitrochlorobenzene (picryl chloride) requires an excess of fuming nitric acid in oleum at elevated temperature. Both are useful for the synthesis of other polynitroarylene explosives but only 2,4-dinitrochlorobenzene finds industrial importance (Sections 4.8.1.2 and 4.8.1.3). 

Whereas in benzene chemistry halogen substituents are ortho-para directing because of their weak donor effects, in thiophene the +M effect is strongest across the 2,3-bond. This means that a 2-chloro group gives... 

Method of Nys and Rekker The Nys and Rekker method [53,54] has been developed for mono- and di-substituted benzenes. The substituents considered are halogen atoms and hydroxyl, ether, amino, nitro, and carboxyl groups, for which contributions have been calculated by multiple regression analysis (s = 0.106, r = 0.994, F = 1405). Rekker discusses the extension of his approach to other compound classes, such as PAHs, pyridines, quinolines, and isoquinolines. 

A Hammett equation was also established for substituted benzenes. A separate model was established for halogenated benzenes. It has been found that halogen substituents behave differently than substituents such as -CH3 and N02 (Hansch and Leo, 1995). For this reason, an accurate comparison of halogenated substituents and other substituents could not be made. 

Simple benzene derivatives show most of the characteristics of benzene, including the moderate band in the 210-nm region and the benzenoid band in the 260-nm region. Alkyl and halogen substituents increase the values of Amax by about 5 nm, as shown by the examples in Table 16-2. An additional conjugated double bond can increase the value of Amax by about 30 nm, as shown by the UV spectrum of styrene in Figure 16-19. 

On heating in polyphosphoric acid 1-phenylthiosemicarbazides with alkyl or halogen substituent in the benzene ring turn into 2-aminobenzothiazoles in good yield (Scheme 2.101) [578],... 

Chlorination proceeds by a similar mechanism. Reactions that introduce a halogen substituent on a benzene ring are widely used, and many halogenated aromatic compounds with a range of biological activity have been synthesized, as shown in Figure 18.3. 

Returning to Table 12.2, notice that halogen substituents direct an incoming electrophile to the ortho and para positions but deactivate the ring toward substitution. Nitration of chlorobenzene is a typical example of electrophilic aromatic substitution in a haloben-zene its rate is some 30 times slower than the corresponding nitration of benzene. The major products are o-chloronitrobenzene and p-chloronitrobenzene. 

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