Benzene with heteroaromatic compounds

Table 3.17 Values of S.N and for Reaction of CI2 with Benzene and Heteroaromatic Compounds...

In addition to benzene and naphthalene derivatives, heteroaromatic compounds such as ferrocene[232, furan, thiophene, selenophene[233,234], and cyclobutadiene iron carbonyl complexpSS] react with alkenes to give vinyl heterocydes. The ease of the reaction of styrene with sub.stituted benzenes to give stilbene derivatives 260 increases in the order benzene < naphthalene < ferrocene < furan. The effect of substituents in this reaction is similar to that in the electrophilic aromatic substitution reactions[236]. 

Diazo coupling involves the N exocyclic atom of the diazonium salt, which acts as an electrophilic center. The diazonium salts of thiazoles couple with a-naphthol (605). 2-nitroresorcinol (606), pyrocatechol (607-609), 2.6-dihydroxy 4-methyl-5-cyanopyridine (610). and other heteroaromatic compounds (404. 611) (Scheme 188). The rates of coupling between 2-diazothicizolium salts and 2-naphthol-3.6-disulfonic acid were measured spectrophotometrically and found to be slower than that of 2-diazopyridinium salts but faster than that of benzene diazonium salts (561 i. The bis-diazonium salt of bis(2-amino-4-methylthiazole) couples with /3-naphthol to give 333 (Scheme 189) (612). The products obtained from the diazo coupling are usuallv highly colored (234. 338. 339. 613-616). 

For the introduction of fluorine into aromatic and heteroaromatic compounds the photolytic fluoro-de-diazoniation sometimes has advantages compared with the corresponding thermal dediazoniation (Balz-Schiemann reaction, see Sec. 10.4). For aromatic substrates the reaction was studied by Rutherford et al. (1961), Christie and Paulath (1965), Petterson et al. (1971), and Becker and Israel (1979). Hexafluorophos-phates sometimes give better yields than tetrafluoroborates (Rutherford et al., 1961). In analogy to Balz-Schiemann reactions in solution (Fukuhara et al., 1987), photolytic fluoro-de-diazoniations of benzene derivatives with electron-withdrawing substituents give lower yields. 

The first group consists of monocyclic heteroaromatic compounds with one heteroatom and without strongly electron-donating substitutents (OH, NH2). Pyrrole, furan, and thiophene are better electron donors than benzene. The order of their reactivities in azo coupling is thiophene > pyrrole > furan > benzene. 

Reaction with Aromatic and Heteroaromatic Compounds 4.1 Benzene and its Derivatives... 

In a paper pnblished in the early 1950s Touster found that sodio derivatives of many alkyl-substituted heteroaromatic compounds or of allyl-substituted benzenes 30 can be oximated with alkyl nitrites in refluxing anhydrous liquid ammonia at atmospheric pressure... 

Subsequently, Kato and Goto have reported the synthesis of 2- and 4-pyridinecarbox-aldoximes from 2- and 4-picoline with potassium amide and amyl nitrite in liquid ammonia at — 33°C, although they failed to obtain either of these oximes when the reaction was carried ont with sodium amide in liquid ammonia at room temperature in a sealed tube. Finally, in 1964, aUcyl-substituted heteroaromatic compounds and allyl-substituted benzenes were oximated in liquid ammonia at —33 °C with sodamide and an alkyl nitrite . 

The products of the electrochemical perfluorination of aromatic and heteroaromatic compounds are the corresponding perfluorinated cyclic and heterocyclic alkanes.28 and also per-fluorinated derivatives of the heteroaromatic compounds. Perfluorocyclohexane is the principal product from the electrochemical fluorination of benzene and fluorobenzene. Chloro derivatives of perfluorocyclohexane are produced from chlorobenzenes. Anisoles give fully saturated per-fluoro ethers, together with cleavage products. Extensive cleavage is observed in the fluorination of benzenethiols. Chloropyridines, fluorocarbons and sulfur hexafluoride or nitrogen trifluoride are characteristic byproducts from the above scries of reactions. 

Solvent effects on relative rate constants are also usually small. When a heteroaromatic compound quaternizes at more than one site, for example, the product ratio can be insensitive to solvent variations. A constant isomer ratio is recorded for methylation (Mel) of 3-/erf-butyl-6-dimethylaminopyridazine (10), in hexane, benzene, carbon tetrachloride, acetone, and acetonitrile, but not in dimethoxyethane or tetrahydrofuran. The suggestion was made that Mel may have reacted with the last two ether solvents to give an oxonium ion. Since the identity of the quaternizing agent changes, the product ratio varies as well.13... 

Several types of nitrogen-containing heteroaromatic compounds are also capable of producing carboxonium-centered dications (Table 3).45 Among the dications 108-113, all have been shown to react with weak nucleophiles such as benzene, deactivated arenes, and even saturated hydrocarbons. Moreover, their reactivities greatly exceed that of comparable monocationic electrophiles. In the case of dication 111, for example, it is shown that it will condense with benzene in a hydroxyalkylative conversion (eq 36).45d... 

The observed electrophilic reactivity is indicative of superelectrophilic activation in the dication 173. Other ammonium-carboxonium dications have also been reported in the literature, some of which have been shown to react with benzene or other weak nucleophiles (Table 4).1 42b 57-60 Besides ammonium-carboxonium dications (175-179), a variety of N-heteroaromatic systems (180-185) have been reported. Several of the dicationic species have been directly observed by low-temperature NMR, including 176, 178-180, 183, and 185. Both acidic (175, 180-185) and non-acidic carboxonium (176-177) dicationic systems have been shown to possess superelectrophilic reactivity. The quinonemethide-type dication (178) arises from the important biomolecule adrenaline upon reaction in superacid (entry 4). The failure of dication 178 to react with aromatic compounds (like benzene) suggests only a modest amount of superelectrophilic activation. An interesting study was done with aminobutyric acid... 

Mesylates are used for Ni-catalysed reactions. Arenediazodium salts 2 are very reactive pseudohalides undergoing facile oxidative addition to Pd(0). They are more easily available than aryl iodides or triflates. Also, acyl (aroyl) halides 4 and aroyl anhydrides 5 behave as pseudohalides after decarbonylation under certain conditions. Sulfonyl chlorides 6 react with evolution of SO2. Allylic halides are reactive, but their reactions via 7t-allyl complexes are treated in Chapter 4. Based on the reactions of those pseudohalides, several benzene derivatives such as aniline, phenol, benzoic acid and benzenesulfonic acid can be used for the reaction, in addition to phenyl halides. In Scheme 3.1, reactions of benzene as a parent ring compound are summarized. Needless to say, the reactions can be extended to various aromatic compounds including heteroaromatic compounds whenever their halides and pseudohalides are available. 

Chatani and coworkers reported the effective carbonylation of the C-H bond in the aromatic ring via Ru3(CO)12-catalyzed reaction of olefins and CO with heteroaromatics (Eq. 101) [159] and substituted benzene (Eq. 102) [160]. For more examples of the acylation of five-membered heteroaromatic compound see Ref. [ 161 ]. The reaction is closely related to the process of the ortho alkylation of substituted aromatic compounds and involves an additional step of CO insertion. 

A large and important part of the preparative chemistry of heteroaromatic compounds has been concerned with their electrophilic substitution reactions. Similarities between the chemistry of heteroaromatic compounds and benzenoid derivatives were recognized early, and reactions discovered initially in the benzene series were then applied to various heterocycles. 

Aromatic hydrocarbons, such as benzene add to alkenes using a ruthenium catalyst a catalytic mixture of AuCVAgSbFs, or a rhodium catalyst, and ruthenium complexes catalyze the addition of heteroaromatic compounds, such as pyridine, to alkynes. Such alkylation reactions are clearly reminiscent of the Friedel-Crafts reaction (11-11). Palladium catalysts can also be used to for the addition of aromatic compounds to alkynes, and rhodium catalysts for addition to alkenes (with microwave irradiation). " Note that vinyhdene cyclopropanes react with furans and a palladium catalyst to give aUylically substituted furans. ... 

Moreover, the selenol esters can acylate reactive arenes and heteroaromatic compounds when cop-per(I) triflate is employed as the selenophilic metal cation. - The acylation of aromatics by use of the benzene complex of copper(I) triflate (43 Scheme 12) was complete within an hour at room temperature, with benzene as solvent, and the acylation products were obtained in high yields. Intramolecular acylation was examined successfully, as shown in equation (20). 

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