Nuclear substitution products

Acylated amines and their substitution reactions (Expts 6.67 and 6.68). 

The important spectroscopic features (i.r., p.m.r., m.s., and u.v.-visible) which are observed with the varied range of substitution products of aromatic amines are descriptively discussed under appropriate preparative sections. 

The nuclear substitution reactions that are considered in this section are (a) halogenation, (6) nitrosation, (c) sulphonation and (d) ortho formylation. All 

The free amino group strongly activates the aromatic ring towards electrophilic attack and aromatic substitution of amines often results in polysubstitution. For example, the bromination of aniline yields largely 2,4,6-tribromoaniline (Expt 6.59). 

Monosubstitution of the free amine may be achieved by using a less reactive electrophile. Thus aniline and o-toluidine may be mono-iodinated (Expt 6.60) by treatment with iodine (in the presence of sodium hydrogen carbonate or calcium carbonate to remove the liberated hydrogen iodide), the substituent entering the position para to the amino group. Direct iodination can also be effected by using the more powerfully electrophilic reagent, iodine monochloride 

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Halogenomethyl, hydroxymethyl and aminomethyl groups readily undergo displacement reactions with nucleophilic reagents. Both side-chain and nuclear substitution products have been obtained (Scheme 57). These two possibilities are exemplified by the reaction of furfuryl chloride with sodium cyanide (Scheme 58). 

Benzylsilanes are also oxidized under similar conditions with selective cleavage of the C Si bond (Scheme 4) [24,25], Nucleophiles are introduced onto the benzylic carbon exclusively. Nuclear substitution products are not formed. The high chemoselectivity observed for the reaction of p-(trimethylsilyl)benzyltrimethylsilane is interesting. Only the benzyl C-Si bond is cleaved without affecting the aromatic C-Si bond. 

Reactions between aromatic hydrocarbon radicabcations and cyanide ions, with few exceptions, give low yields of nuclear substitution products [76], In some cases, better results have been obtained by anodic oxidation of the aromatic compound in an emulsion of aqueous sodium cyanide and dichloromethane with tetra-butylammonium hydrogen sulphate as a phase transfer agent [77, 78]. Methoxy-benzenes give exceptionally good yields from reactions in acetonitrile containing tetraethylammonium cyanide, sometimes with displacement of methoxide [79, 80]... 

Bromomethylbenzo[6]thiophenes are readily obtained in high yields by treatment of the corresponding methyl compound with. V-bromosuccinimide in the presence of benzoyl peroxide.91,105,298 343,4i3,447,487,489-492,517,518 Applied to 3-methylbenzo[6]thiophene, this procedure affords 2-bromo-3-methylbenzo[6]thiophene (12%), in addition to the required product the yield of nuclear substituted product rises to 78% when peroxides are excluded.487 When 3,5-dimethylbenzo[6]thiophene is treated with W-bromosuccinimide, the 3-methyl group is preferentially brominated,489 but in the cases of other 5-alkyl-3-methylbenzo[6]thiophenes inseparable mixtures of products are formed.292 The above reaction has also been applied to... 

In the context of the direct mechanism, several perplexing features concerning nuclear and side-chain substitution of aromatic compounds have been highlighted [124-126], and in the search for explanations attempts have been made to estimate, by thermo-chemically based calculations, free energies of activation for reactions between radical cations and nucleophiles. Long-standing puzzles in this area include the dependence of the ratio of side chain/nuclear substituted products on the nucleophile for alkylbenzenes, side-chain acetoxylation predominates in acetic acid (AcOH) unless AcO is present, when nuclear substitution becomes important. 

From a preparative point of view it is of interest to notice that selective nuclear substitution may be obtained when the oxidation is carried out in an undivided cell using a cathode made of Pd/C [114]. With this experimental setup, the side-chain acetoxylated product is reduced back to starting material at the cathode. The nuclear substituted product is unaffected and will accumulate during the electrolysis. 

Many of the reactions of quinoxaline N-oxides are typical of those of heteroaromatic N-oxides in general. Thus the N-oxide function is readily reduced, nuclear substitution products are obtained on treatment with... 

A-Oxides of 2- and 4-alkylpyridines are functionalized in the side-chain by acylating agents (acid anhydrides, sulfonyl chloride, POCI3). For instance, 2- or 4-picoline-l-oxide with acetic anhydride yields a mixture of acetoxy compounds in which the methyl-substituted products, namely 2- and 4-acetoxymethylpyridine, dominate (87 and 90). Some nuclear-substituted products (88, 89, 91) are also formed ... 

Other Applications. Thionyl chloride has been used to convert epoxides to vicinal dichlorides and for the preparation of dialkyl sulfides from Grignard reagents. Phenols react with SOCI2 to produce aryl chlorosulfites and diaryl sulfites or nuclear substitution products. As shown in eq 14, Aluminum Chloride catalysis yields symmetric sulfoxides, while in the absence of Lewis acids, aromatic thiosulfonates are the principal products. Primary amines, especially aromatic ones, react with SOCI2 to produce N-sulfiny lamines, which are potent enophiles and useful precursors to some heterocyclic compounds. ... 

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