Anisole para substitution

Sulphinic acids. Aromatic sulphinic acids are found in Solubility Group II. They may be detected by dissolving in cold concentrated sulphuric acid and adding one drop of phenetole or anisole when a blue colour is produced (Smiles s test), due to the formation of a para-substituted aromatic sulphoxide. Thus the reaction with benzenesulphinic acid is ... 

It has been shown that it is possible to compel regiospecific para substitution by enclosing the substrate molecules in a cavity from which only the para position projects. Anisole was chlorinated in solutions containing a cyclodextrin, a molecule in which the anisole is almost entirely enclosed (see Fig. 3.4). With a high enough concentration of cyclodextrin, it was possible to achieve a para/ortho ratio of 21.6 (in the absence of the cyclodextrin the ratio was only 1.48). This behavior is a model for the regioselectivity found in the action of enzymes. 

Electron-rich aromatic compounds, such as phenol, anisole and A,./V-dimethylaniline, add to bis(2-trichloroethyl) azodicarboxylate under the influence of lithium perchlorate, boron trifluoride etherate or zinc chloride to yield para-substituted products 74, which are transformed into the anilines 75 by means of zinc and acetic acid86. Triflic acid (trifluoromethanesulphonic acid) catalyses the reactions of phenyl azide with benzene, toluene, chlorobenzene and naphthalene, to give TV-arylanilines (equation 34)87. 

Irradiation of 59a,c in benzene gave the corresponding 3-phenylindoles 62 (R = Ph) (66LA17). In the case of the 3-diazo-derivative 59a, a dark red dye having structure 61 was also isolated. Photolysis of 59a in anisole gave the para substitution products 62 (R = 4-OMe-Ph) whereas in ben-zonitrile or methyl benzoate, only dark red oily mixtures were obtained. 

Phenol derivatives have also been oxidized anisole undergoes substitution both in the ortho (30%) and the para position (70%) (Romano et al, 1990). 

These compounds are suggested if sulphur is present. If nitrogen is also present the compound may be an aminosulphonic acid. The infrared spectrum will show absorption at 3400-3200 cm -1 (OH str.) and 1150 and 1050 cm-1 (S=0 str. in a sulphonic add) or at 1090cm-1 (S=0 str. in a sulphinic acid). For derivative preparations for sulphonic acids see Section 9.6.26, p. 1284. The presence of an aromatic sulphinic add may be further confirmed by dissolving in cold concentrated sulphuric add and adding one drop of phenetole or anisole when a blue colour is produced (Smiles s test), due to formation of a para-substituted aromatic sulphoxide. The reaction is ... 

In the case of anisole, the reaction takes following route shown in Scheme 4-10. The reaction yields only products of the ortho and para substitutions the meta isomer is lacking. If it were a standard radical substitution, the meta isomer would obviously be formed in a certain amount (i.e., in the same amount as that for ortho-substituted product). 

The degradation of the anisoles was found to follow pseudo first-order degradation. The apparent first-order rate constant (/c,. ) was compared to Hammett s constant to determine if a correlation existed between the degradation of mete-substituted and para-substituted anisoles. Removal rates were greater that 80%, and for fluoroanisole and aminoanisole they were 100%. 

A correlation for less structurally related compounds was also developed by Amalric et al. (1996). To develop this correlation, meta- and para-substituted anisoles were studied. These aromatic compounds were substituted with F, Cl, N02, OH, and NH2 groups. The first-order degradation rate constant, kapf was predicted with the octanol/water partition coefficient (log Kow), Brown s constant (o+), and molar refractivity (MR) used as descriptors. The following correlation was developed ... 

Experimental and Predicted Values of Meta- and Para-Substituted Anisoles... 

In reactions involving disubstitution of anisole, the better strategy is to introduce the para substituent first. The methoxy group is ortho, para-directing, but para substitution predominates. 

Methoxybenzene (anisole), 1,2-dimethoxybenzene, and similar aromatic ethers react with S2CI2 in dry ether or benzene at 0-20 °C within several days to give a mixtnre of bisarylsulfanes R2S with n = 1-3 (eqnation 29). Anisole is substituted in the para position. ... 

The tetrafluoroborate from (37) serves as a source of 4-nitrophenyl-sulphenium ion (p-N02C6H4S ), which can attack anisole to give a para-substituted product. 

Thallium carboxylates, particularly the acetate and trifluoroacetate, which can be obtained by dissolution of the oxide in the acid, are extensively used in organic chemistry.14 Both Tl metal and Tl1 salts such as the acetylaceton-ate also have specific uses. One example is the use of thallium(m) acetate in controlled bromination of organic substances such as anisole. The trifluoroacetate will directly thallate (cf. aromatic mercuration, Section 18-9) aromatic compounds to give aryl thallium ditrifluoroacetates, e.g., C6H5Tl(OOCCF3)2. It also acts as an oxidant, inter alia converting para-substituted phenols into p-quinones. 

Table 12.9. The ortho Effect and ortho-para Substitution in Friedel-Crafts Reactions of Anisole and Toluene...

Other arenechromium tricarbonyls. Semmelhack has extended his study of the reactions of carbanions with benzenechromium tricarbonyl to anisole-and toluenechromium tricarbonyl. The distribution of products depends on the particular anion used, but almost complete absence of para-substitution is consistently observed. A preference for meta-substitution over orfAo-substitution is general. 

Thermal treatment of the dimer with anisole, toluene, and 1-chloronaphtha-lene in the presence of a large excess of pTsOH and air leads to the formation of mono-arylated azafullerenes in 78-90% isolated yields [68]. The reaction with anisole and toluene yield para-substitution products 35 and 39, while 1-chloro-naphthalene is substituted at various positions (Fig. 21). The reaction does not take place in the absence of air or pTsOH. The reaction is presumed to proceed through electrophilic aromatic substitution by C59N, which was proposed as being formed via thermal homolysis of the dimer, followed by oxidation with O2. 

Michael additions are accessed upon reaction of TpRe(CO)(L)(5,6- -anisole) and substituted anisole complexes with various Michael aceeptors such as methylvinylketone (MVK), 3-penten-2-one, 2-cyclopentenone, 2-cyclohexenone, NMM or methylpropenoate in the presence of a Lewis acid (e.g., BF3 OEt2 Scheme 42). Addition at the para carbon occurs anti to the metal center. 

Relative reactivity studies of homolytic substitution of monosubstituted benzene derivatives reveal that the 1-adamantyl radical has more pronounced nucleophilic properties than have other, more strained, bridgehead radicals. With benzo-nitrile 21.1) almost exclusive para-substitution is observed, whereas with anisole 0.65) the three possible sites are attacked almost equally. Kinetic studies on the reaction of adamantanethione with adamantane-2-thiol indicate that the rate-controlling chain-propagation step is hydrogen abstraction from the thiol (AdHSH) by the carbon-centred radical AdHSSAd-, and that the main mode of termination involves the diffusion-controlled bimolecular self-reaction of these radicals. ... 

In a related study,the effect of attaching para-substituted phenyl groups directly to the 2-position of the 4-phenyl-l,3-dithiolium cation has been examined. As expected, electron-rich aryl groups tend to stabilize the cations in water. The methods used for the preparation of the 2-aryl-l,3-dithiolium salts (66) are of interest. These include the action of Grignard reagents on 2-methoxy-4-phenyl-l,3-dithiole (65) followed by hydride abstraction with triphenylmethyl perchlorate, and the reaction of 4-phenyl-1,3-dithiolium perchlorate (67) with appropriately activated benzene derivatives (e.g. phenol, anisole, and aniline). Treatment of 2-p-hydroxy-phenyl-4-phenyl-l,3-dithiolium perchlorate with triethylamine yields the red quinonoid compound (68). 

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