Substitution reactions at aromatic

Aromatic substitution (see Substitution reactions at aromatic carbon atoms) Aromatization of six-membered rings Titanium(IV) chloride-Diethylaluminum chloride, 309... 

Substitution reactions at aromatic carbon (see also Reduction reactions, Ullmann ether coupling, specific reactions such as Nitration) Arene(tricarbonyl)chromium complexes, 19... 

Substitution at the Alcohol Group. Acylation of the OH group by acylating agents such as acid chlorides or anhydrides is one of the important high yielding substitution reactions at the OH group of lactic acid and its functional derivatives. AUphatic, aromatic, and other substituted derivatives can be produced. 

Arenediazonium ions 1 can undergo a coupling reaction with electron-rich aromatic compounds 2 like aryl amines and phenols to yield azo compounds 3. The substitution reaction at the aromatic system 2 usually takes place para to the activating group probably for steric reasons. If the para position is already occupied by a substituent, the new substitution takes place ortho to the activating group. 

Other electrophilic substitution reactions on aromatic and heteroaromatic systems are summarized in Scheme 6.143. Friedel-Crafts alkylation of N,N-dimethyl-aniline with squaric acid dichloride was accomplished by heating the two components in dichloromethane at 120 °C in the absence of a Lewis acid catalyst to provide a 23% yield of the 2-aryl-l-chlorocydobut-l-ene-3,4-dione product (Scheme 6.143 a) [281]. Hydrolysis of the monochloride provided a 2-aryl-l-hydroxycyclobut-l-ene-3,4-dione, an inhibitor of protein tyrosine phosphatases [281], Formylation of 4-chloro-3-nitrophenol with hexamethylenetetramine and trifluoroacetic acid (TFA) at 115 °C for 5 h furnished the corresponding benzaldehyde in 43% yield, which was further manipulated into a benzofuran derivative (Scheme 6.143b) [282]. 4-Chloro-5-bromo-pyrazolopyrimidine is an important intermediate in the synthesis of pyrazolopyrimi-dine derivatives showing activity against multiple kinase subfamilies (see also Scheme 6.20) and can be rapidly prepared from 4-chloropyrazolopyrimidine and N-bromosuccinimide (NBS) by microwave irradiation in acetonitrile (Scheme... 

The controlled occurrence of two electrophilic aromatic substitution reactions at a single phosphorus center using phosphorus trichloride has been accomplished using aluminum chloride as the catalyst, but with tris(2-chloroethyl) phosphite as the agent for the decomposition of the adduct-Lewis acid complex (Figure 6.13).60... 

The main problem encountered during electrophilic substitution reactions of aromatic amines is that of their veiy high reactivity. Substitution tends to occur at ortho- and para-positions. If we have to prepare monosubstituted aniline derivative, how can the activating effect of -NH group be controlled This can be done by protecting the -NH group by acetylation with acetic anhydride, then carrying out the desired substitution followed by hydrolysis of the substituted amide to the substituted amine. 

The most common methods suitable for the synthesis of different azolium compounds will be discussed here. Two routes are particularly useful for the preparation of the imidazolium salts (1) substitution reactions at the nitrogen atoms of imidazole [25] and (2) multicomponent reactions for the generation of an Af,Af -substituted heterocycle which are particularly useful for the synthesis of imidazolium salts bearing aromatic, very bulky, or particularly reactive N,N -sub-stituents (Fig. 3a,b) [26]. Both methods offer the opportunity to produce unsym-metrically substituted imidazolium salts of type 1 either by stepwise alkylation of imidazole or by the synthesis of an W-arylated imidazole derivative followed by 77 -alkylation [27]. Nevertheless, the method of choice for the preparation of the imidazolium salts 1 is the 77,77 -substitution of imidazole. Several other methods for the preparation of imidazolium salts with previously unattainable substitution patterns have also been described [28, 29]. 

Anodic substitution reactions of aromatic hydrocarbons have been known since around 1900 [29, 30]. The course of these processes was established primarily by a study of the reaction between naphthalene and acetate ions. Oxidation of naphthalene in the presence of acetate gives 1-acetoxynaphthalene and this was at first taken to indicate trapping of the acetyl radical formed during Kolbe electrolysis of... 

This process is an example of the ability of nickel complexes to catalyze substitution reactions of aromatic halides under very mild conditions. A further example of their catalytic activity is the carbonylation of aromatic halides at the atmospheric pressure of carbon monoxide (6). 

In keeping with its aromatic character and unsymmetrical charge distribution, azulene undergoes certain typical electrophilic substitution reactions at the 1 and 3 positions. Thus Friedel-Crafts acylation leads to a mixture of 1-ethanoylazulene and 1,3-diethanoylazulene ... 

B-2,6-Dimethylarylborazines have not been obtained in a direct borazine synthesis, though they can be prepared by Grignard arylation of l,3,5-trimethyl-2,4,6-trichloroborazine 01.92), These compounds show high hydrolytic stability, even in acid and basic medium, and they can be subjected to substitution reactions at the aromatic sites 91>. For example, free radical bromination 93> or Friedel-Crafts acetylation 94> has been accomplished. 

Free-Radical Induced Bond Formation and Aromatization. Based on current understanding of free-radical aromatic substitution reactions at low temperatures ( 7), a major pathway for polymerization and crosslink formation in coal systems is expected to be,... 

Conjugate substitution electrophilic alkenes bearing leaving groups can promote substitution reactions at C=C related to those at C=0 Nucleophilic aromatic substitution electron-poor aromatic rings that allow substitution reactions with nucleophiles rather than the usual electrophiles... 

Replacement of aliphatic hydrogens with bromine can be done under free radical substitution conditions, but reaction at aromatic carbons is unfavorable because of the very high energy of the aryl radical. Benzylic substitution is usually the only product observed. 

Isatin is a stable, bright orange solid that is commercially available in large quantities. Because it readily undergoes clean aromatic substitution reactions at C-5, iV-alkylation via an anion, and ketonic reactions at the C-3-carbonyl group, for example enolate addition, it is a very useful intermediate for the synthesis of indoles and other heterocycles. 

Polycyclic arene(tricarbonyl)chromium complexes.h These complexes arc best prepared by treatment of polycyclic arcnes with (NHj),CT(CO)37 and BFj ethcratc. As in complcxation with Cr(CO), the terminal or most aromatic ring is complexed selectively. However, the lower temperatures used in the newer method are advantageous with thermally labile polycyclic arcnes. These complexes are useful for substitution reactions at positions that arc not available by electrophilic substitution of the arenc directly. One such reaction is hydroxylation effected by simultaneous reaction with a base (BuLi or I. DA) and tributoxyborane (excess) followed by H2O2/HOAC workup. Rcgiosclectivc silylation is effected by reaction of the complex with LiTMP and (CHj SiCI with... 

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