Halogenated benzenes disubstituted

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. 

Pyridinones and quinolinones undergo electrophilic attack at the (3 -position (12,13) fairly easily and disubstitution is well known in the pyridine series. Pyridinones are more easily halogenated than benzene, but the highly acidic conditions used for nitration and sulfonation makes these less easy reactions. Electrophiles also attack at the oxygen (14), but this is considered as a substituent reaction and therefore will be dealt with in Chapter 2.06. 

As an alternative to the diradical ring closure that occurs with the 3 -indazole ring contraction, the employment of a 1,3-elimination from an ortho, a-disubstituted aromatic has much appeal for cycloproparene formation, not least because of the simplicity of the process and the ready availability of the starting materials. It is not surprising, therefore, that such a report appeared as early as 1974. Radlick and Crawford found that 1-bromo-2-(methoxymethyl)benzene (33) underwent lithium-halogen exchanged and cyclization to 1 upon treatment with butyllithium. The yield was a modest but acceptable 30%. In similar vein, the cyclization methodology provided rocketene (34) albeit in 5% yield (equation 7a). ... 

Increasing the reaction temperature and the amount of halogen used results in the introduction of further halogen atoms. It was noted in Chapter 2 that the halogen atom in chlorobenzene is ortholpara directing, but deactivating to electrophilic substitution as a result of opposing mesomeric (+M) and inductive (-1) effects. Consequently, disubstitution leads to a mixture of the 1,2- and, mainly, 1,4-isomers under conditions similar to those required to attack benzene. 

Constancy of A/ Values for Halogen SubstituentsxSrtvB net Adsorption of Monosubstituted and />ara-Disubstitut --Benzenes on 0.7% H2O-AI2O3 from Pentane... 

Halogen atoms activated by carbonyl groups adjacent to the benzene ring can be, in some cases, displaced with nucleophiles. For example, compound (250) treated with iV,A(-dimethylaminopropyl amine gives the product of monosubstitution (251) together with the rearrangement 2 1 product (252). No product of normal disubstitution is formed (Equation (34)) <92CPB2905>. 

Halogenation of thiophene occurs very readily at room temperature and is rapid even at — 30°C in the dark higher temperatures give rise to polysubstitution and even addition products. The rate of halogenation of thiophene, at 25°C, is about 10 times that of benzene. 2-Bromo- and 2-iodothiophene can be produced cleanly under various controlled conditions, free from 2,5-disubstituted product which is always present in chlorinations. 

Optical activity, retention in the Stevens rearrangement 418 Optical-rotatory dispersion, in configuration assignment 136 of amino acids 134, 135 Orientational control, in exchange reactions 260 in halogenation 257, 263 in tritylation 263 of disubstituted benzenes 263 Orientational effect 250, 251 Orton rearrangement 637 Oxamidinium salts 734—737 from tetraaminoethylencs 721, 722 hydrolysis of 731... 

Some data relating to orientation of disubstituted benzenes are shown in Table 26. Thus the halogenation and tritylation ° of aniline derivatives results in substitution chiefly as expected fi om the -f-iZ effect. References on nitration and sulphonation have not been included in Table 26, since these processes often lead to oxidation products, making the orientational comparison in these compounds doubtful. 

---