Toluene Chlorine substitution products

Chlorine Substitution Products of Toluene.—Taking toluene, the first of the benzene homologues, as an illustration we have the following possible mono-chlorine substitution products, all of which are known. 

These chlorine substitution products of toluene are known as chlor-toluenes because all of them still have the toluene character, i.e. a benzene ring in which one hydrogen is substituted by methyl. 

Isomerism of the tri- and tetra- substituted toluenes will not be considered at length. The chlorine substitution products in which more than one chlorine is substituted may likewise occur in still another isomeric form. Instead of the two chlorines or other substituting elements or groups both entering the ring or the side chain, we may have compounds in which one or more elements enter one position, and at the same time, one or more enter the other position. Such compounds are known, but will simply be mentioned by formula, e.g. 

These effects can be attributed mainly to the inductive nature of the chlorine atoms, which reduces the electron density at position 4 and increases polarization of the 3,4-double bond. The dual reactivity of the chloropteridines has been further confirmed by the preparation of new adducts and substitution products. The addition reaction competes successfully, in a preparative sense, with the substitution reaction, if the latter is slowed down by a low temperature and a non-polar solvent. Compounds (12) and (13) react with dry ammonia in benzene at 5 °C to yield the 3,4-adducts (IS), which were shown by IR spectroscopy to contain little or none of the corresponding substitution product. The adducts decompose slowly in air and almost instantaneously in water or ethanol to give the original chloropteridine and ammonia. Certain other amines behave similarly, forming adducts which can be stored for a few days at -20 °C. Treatment of (12) and (13) in acetone with hydrogen sulfide or toluene-a-thiol gives adducts of the same type. 

Ring opening of ortho adducts may also have occurred in the experiments reported by Perrins and Simons [192], who irradiated benzene, toluene, and anisole in the presence of dichloroethenes (all isomers), trichloroethene, and tetrachloroethene. The products were chlorine-substituted linear tetraenes, but no ortho adducts were found. An analogous reaction occurred with benzonitrile and 2-methylbut-2-ene, but, in contrast to the results reported by Atkinson et al. [73], the ortho adduct was not detected. 

The higher homologues of toluene such as ethylbenzene are not usually halogenated selectively and mixtures are often produced (see Chapter 3). In the case of ethylbenzene itself, the major product of chlorination is the 1-substituted product (56%). Bromine is more selective and the 1-bromo derivative 7 is formed exclusively. 

The chlorination of toluene in the absence of catalysts that promote nuclear substitution occurs preferentially in the side chain. The reaction is promoted by free-radical initiators such as ultraviolet light or peroxides. Chlorination takes place in a stepwise manner and can be controlled to give good yields of the intermediate chlorination products. Small amounts of sequestering agents are sometimes used to remove trace amounts of heavy-metal ions that cause ring chlorination. 

The various methods that are used for the production of aromatic acids from the corresponding substituted toluenes are outlined in Figure 1. The first two methods -chlorination/hydrolysis and nitric acid oxidation - have the disadvantage of relatively low atom utilization (ref. 13) with the concomitant inorganic salt production. Catalytic autoxidation, in contrast, has an atom utilization of 87% (for Ar=Ph) and produces no inorganic salts and no chlorinated or nitrated byproducts. It consumes only the cheap raw material, oxygen, and produces water as the only byproduct. 

Via such a gas/liquid reaction, toluene-2,4-diisocyanate reacts with chlorine to give l-chloromethyl-2,4-diisocyanatobenzene [6], As a ring-substituted side product, toluene-5-chloro-2,4-diisocyanate is formed in minor quantities. 

Furosemide can also be synthesized starting with 2,4-dichlorobenzoic acid (formed by chlorination and oxidation of toluene). Reaction with chlorosulfonic acid is an electrophilic aromatic substitution via the species -S02C1 attacking ortho and para to the chlorines and meta to the carboxy-late. Ammonolysis to the sulfonamide is followed by nucleophilic aromatic substitution of the less hindered chlorine by furfurylamine (obtained from furfural—a product obtained by the hydrolysis of carbohydrates). 

The reaction of toluene-2,4-diisocyanate with chlorine to l-chloromethyl-2,4-diisocyanatobenzene was carried out in a falling-film microstructured reactor with a transparent window for irradiation [264]. There are two modes of reaction. The desired radical process proceeds with the photoinduced homolytic cleavage of the chlorine molecules, and the chlorine radical reacts with the side chain of the aromatic compound. At very high chlorine concentrations radical recombination becomes dominant and consecutive processes such as dichlorination of the side chain may occur as well. Another undesired pathway is the electrophilic ring substitution to toluene-5-chloro-2,4-diisocyanate, promoted by Lewis acidic catalysts in polar solvents at low temperature. Even small metallic impurities probably from corrosion of the reactor material can enhance the formation of electrophilic by-products. 

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