Benzene derivatives . See

It should be pointed out that the existence of stable structures of the intermediate-complex type (also known as a-complexes or Wheland complexes) is not of itself evidence for their being obligate intermediates in aromatic nucleophilic substitution. The lack of an element effect is suggested, but not established as in benzene derivatives (see Sections I,D,2 and II, D). The activated order of halogen reactivity F > Cl Br I has been observed in quantita-tivei36a,i37 Tables II, VII-XIII) and in many qualitative studies (see Section II, D). The reverse sequence applies to some less-activated compounds such as 3-halopyridines, but not in general.Bimolecular kinetics has been established by Chapman and others (Sections III, A and IV, A) for various reactions. 

General Procedure for the Formation of Benzene Derivatives (see Eq. 2.48) At 0°C, dimethyl acetylenedicarboxylate (284 mg, 2 mmol) and CuCl (198 mg, 2 mmol) were added to a solution of zirconacyclopentadiene (1 mmol) in THF, prepared in situ according to the known procedure [12]. The reaction mixture was then allowed to warm to room temperature and was stirred for 1 h. After hydrolysis with 3 n HC1, the mixture was extracted with diethyl ether. The combined extracts were washed sequentially with water, aq. NaHC03 solution, brine, and water, and then dried over MgS04. Concentration in vacuo followed by flash-chromatography eluting with a mixture of hexane and diethyl ether (10 %) afforded benzene derivatives. 

For a review of this and closely related reactions, see Morrison, in Feuer The Chemistry of the Nitro and Nitroso Groups, pt. 1 Wiley New York, 1969, pp. 165-213, 185-191. For a review of photochemical rearrangements of benzene derivatives, see Kaupp Angew. Chem. Int. Ed. Engl. 1980, 19, 243-275 [Angew. Chem. 92, 245-276). See also Yip Sharma Res. Chem. Intermed. 1989, 11, 109. 

The only exception to this rule concerns the mercuration reaction, but there are good reasons to believe that mercuration of thiophene derivatives occurs by a mechanism different from that in benzene derivatives (see Section II, F, 2). 

Fragmentation of an adduct with release of a nitrile, CO2 or N2 are most common and the latter provide an irreversible method for the formation of a new diene or aromatic compound. Cycloaddition of a pyran-2-one or a 1,2-diazine (pyridazine) with an alkyne gives an intermediate bridged compoimd that loses CO2 or N2 to generate a benzene derivative (see Scheme 3.46). Many other aromatic and heteroaromatic compounds can be prepared likewise. For example, a synthesis of lavendamycin made use of the inverse electron demand Diels-Alder reaction between the 1,2,4-triazine 116 and the enamine 117, followed by in situ elimination of pyrrolidine and retro Diels-Alder reaction, releasing N2 and the substituted pyridine 118 (3.88). 2... 

When a sulfonamide reacts with aqueous acid or aqueous hydroxide, the amine (or ammonia) is released along with the parent sulfonic acid. Butanesulfonamide (191), for example, reacts with aqueous hydroxide (followed by an acid neutralization step) to give butanesulfonic acid (190) and ammonia. Sulfonamides are quite stable molecules and they are used in a variety of applications, particularly those sulfonamides derived from benzene derivatives (see Chapter 21). Sulfanilamide (192), for example, is a potent antibacterial agent and isobuzole (193), with the formal name of JV-(5-isobutyl-l,3,4-thiadiazol-2-yl)-p-methoxy-benzenesulfonamide, has hypoglycemic (antidiabetic) properties. 

Simple cyclobutanes do not readily undergo such reactions, but cyclobutenes do. Ben-zocyclobutene derivatives tend to open to give extremely reactive dienes, namely ortho-c]uin(xlimethanes (examples of syntheses see on p. 280, 281, and 297). Benzocyclobutenes and related compounds are obtained by high-temperature elimination reactions of bicyclic benzene derivatives such as 3-isochromanone (C.W. Spangler, 1973, 1976, 1977), or more conveniently in the laboratory, by Diels-Alder reactions (R.P. Thummel, 1974) or by cycliza-tions of silylated acetylenes with 1,5-hexadiynes in the presence of (cyclopentadienyl)dicarbo-nylcobalt (W.G, Aalbersberg, 1975 R.P. Thummel, 1980). 

This reaction sequence is much less prone to difficulties with isomerizations since the pyridine-like carbons of dipyrromethenes do not add protons. Yields are often low, however, since the intermediates do not survive the high temperatures. The more reactive, faster but less reliable system is certainly provided by the dipyrromethanes, in which the reactivity of the pyrrole units is comparable to activated benzene derivatives such as phenol or aniline. The situation is comparable with that found in peptide synthesis where the slow azide method gives cleaner products than the fast DCC-promoted condensations (see p. 234). 

Ring enlargement of benzene derivatives by carbenes generated from diazo compounds (better in the presence of a Rh catalyst) Conversion of aldehydes to ketones by diazo compounds (Schlotterbeck) see also Ptau Planer... 

Table 18-IV shows the structures of a few simple benzene derivatives that are important commercial products. Study these structures so that you can see their relationship with the simple compounds from which they are derived.

A second reaction which is very often used for the preparation of phthalonitriles, although the yields are usually not reproducible, is the Rosenmund-von Braun reaction (see Houben-Weyl, Vol. E5, p 1460).106 107 Herein, a benzene derivative with a 1,2-dibromidc or 1,2-dich-loride unit is treated with copper(I) cyanide in dimethylformamidc or pyridine. During this reaction the formation of the respective copper phthalocyanine often occurs. This can be used as an easy procedure for the exclusive synthesis of copper phthalocyanines (see Section 2.1.1.7.),1 os-109 but can also lead to problems if the phthalonitrile is required as the product. For example, if l,2-dibromo-4-trifluoromethyl-benzene is subjected to a Rosenmund-von Braun reaction no 4-trifluoromethylphthalonitrile but only copper tetra(tri-fluoromethyljphthalocyanine is isolated.110... 

Hammett discovered linear relationships between two sets of equilibrium or rate constants of substituted benzene derivatives (reviews Hammett 1937, 1940, 1970, Johnson 1973, Exner 1988, and others see Scheme 7-1). 

Hydro-de-diazoniation seems to be an unnecessary reaction from the synthetic standpoint, as arenediazonium salts are obtained from the respective amines, reagents that are normally synthesized from the hydrocarbon. Some aromatic compounds, however, cannot be synthesized by straightforward electrophilic aromatic substitution examples of these are the 1,3,5-trichloro- and -tribromobenzenes (see below). These simple benzene derivatives are synthesized from aniline via halogenation, diazotization and hydro-de-diazoniation. Furthermore hydro-de-diazoniation is useful for the introduction of a hydrogen isotope in specific positions. 

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. 

In Brown s classification a diazonium ion is a reagent of very low reactivity and correspondingly high substrate selectivity and regioselectivity. This follows from the fact that benzenediazonium salts do not normally react with weakly nucleophilic benzene derivatives such as toluene. More reactive heteroaromatic diazonium ions such as substituted imidazole-2-diazonium ions will even react with benzene (see Sec. 12.5). 

Comparison (Tables 7-9) shows that 47 and 48 are similar in their host properties, but they are not equivalent in hehavior. Thus, host compound 48 is more qualified to select according to spatial aspects (see benzene derivatives) and, as a rule, it also forms the thermally more stable inclusions. This may be attributed to the rigid molecular geometry of the spirane 48, whereas the biaryl 47 allows sterical adaptation to different guests via the flexible hinge to a certain degree. 

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