Nitrates sulfonate

Thiazole Nitration Sulfonation Brominadon Mercuration Alkylation... 

All the halogenothiazoles, depending on the electron-withdrawing power of the halosubstituent, together with the electron-withdrawing power of the azasubstituent, are only slightly susceptible to electrophilic substitution reactions such as nitration, sulfonation, and so on, while the polyhalogenatjon reaction can take place. 

No simple electrophilic substitution, for example nitrosation, nitration, sulfonation or halogenation of a C—H bond, has so far been recorded in the pteridine series. The strong 7T-electron deficiency of this nitrogen heterocycle opposes such electrophilic attack, which would require a high-energy transition state of low stability. 

In compounds with a fused benzene ring, electrophilic substitution on carbon usually occurs in the benzenoid ring in preference to the heterocyclic ring. Frequently the orientation of substitution in these compounds parallels that in naphthalene. Conditions are often similar to those used for benzene itself. The actual position attacked varies compare formulae (341)-(346) where the orientation is shown for nitration sulfonation is usually similar for reasons which are not well understood. 

The general discussion (Section 4.02.1.4.1) on reactivity and orientation in azoles should be consulted as some of the conclusions reported therein are germane to this discussion. Pyrazole is less reactive towards electrophiles than pyrrole. As a neutral molecule it reacts as readily as benzene and, as an anion, as readily as phenol (diazo coupling, nitrosation, etc.). Pyrazole cations, formed in strong acidic media, show a pronounced deactivation (nitration, sulfonation, Friedel-Crafts reactions, etc.). For the same reasons quaternary pyrazolium salts normally do not react with electrophiles. 

Isoxazoles are presently known to undergo hydrogen exchange, nitration, sulfonation, halogenation, chloroalkylation, hydroxymethylation, Vilsmeier-Haack formylation, and mercuration. The Friedel-Crafts reaction on the isoxazole nucleus has not yet been reported. 

The hydroxyl group is a strongly activating, ortho- and para-directing substituent in electrophilic aromatic substitution reactions (Section 16.4). As a result, phenols are highly reactive substrates for electrophilic halogenation, nitration, sulfonation, and lTiedel-Crafts reactions. 

The chemistry of pyrrole is similar to that of activated benzene rings. In general, however, the heterocycles are more reactive toward electrophiles than benzene rings are, and low temperatures are often necessary to control the reactions. Halogenation, nitration, sulfonation, and Friedel-Crafts acylation can all be accomplished. For example ... 

A commonly used strategy for the higher nitration of phenolic substrates is to sulfonate the electron-rich aromatic ring before nitration. Sulfonic acid groups are electron withdrawing and... 

For the same reasons as outlined for pyrrole (Section 6.1.2), there is preference for 2- rather than 3-substitution. However, conventional electrophilic reactions, such as nitration, sulfonation, etc., carried out under acidic conditions, are very difficult to control. 

The syntheses of iron isonitrile complexes and the reactions of these complexes are reviewed. Nucleophilic reagents polymerize iron isonitrile complexes, displace the isonitrile ligand from the complex, or are alkylated by the complexes. Nitration, sulfonation, alkylation, and bromina-tion of the aromatic rings in a benzyl isonitrile complex are very rapid and the substituent is introduced mainly in the para position. The cyano group in cyanopentakis(benzyl isonitrile)-iron(ll) bromide exhibits a weak "trans" effect-With formaldehyde in sulfuric acid, benzyl isonitrile complexes yield polymeric compositions. One such composition contains an ethane linkage, suggesting dimerization of the transitory benzyl radicals. Measurements of the conductivities of benzyl isonitrile iron complexes indicate a wide range of A f (1.26 e.v.) and o-o (1023 ohm-1 cm.—1) but no definite relationship between the reactivities of these complexes and their conductivities. 

Early workers appeared to show that electrophilic substitution reactions could not be carried out on porphyrins, and began to question the aromaticity of porphyrins since this classical pre-requisite of aromatic character could not be accomplished. However, they had concentrated on reactions of metal-free systems, and since many electrophilic substitution reactions utilize acidic conditions (nitration, sulfonation), they were actually dealing with the non-nucleophilic porphyrin dication. But, as early as 1929, H. Fischer had realised that diacetylation of deuteroporphyrin-IX (Table 1) had to be carried out on a metal complex, such as the iron (III) derivative chelation with a metal ion which cannot be removed under the acid conditions of the subsequent reaction, effectively eliminates dication formation. A judicious choice of metal complex therefore needs to be made for any particular reaction. For example, though magnesium(II) produces an extremely reactive substrate for electrophilic substitution reactions, it is removed by contact with the mildest of acids and is, consequently, of little use for this purpose. 

Biphenyl and terphenyls may be regarded as substituted benzenes that undergo acylation, alkylation, halogenation, nitration, sulfonation, and other reactions common to benzene. The points of initial attack on chlorination, miration, and sulfonation of biphenyl occur at the 2- and 4-positions the latter group predominates. 

The features of the electronic structure of aryl-substituted pyrazolines influence their chemical properties. For example, in the case of 3-substituted 7V-phenyl-pyrazolines 100 reactions of formylation, acylation, nitration, sulfonation, azocoupling and other electrophilic processes involve the para position of the 7V-phenyl ring, with formation of compounds 101 [103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113]. On the other hand, some electrophilic reactions, including nitration, bromination, chlorination, formylation and azocoupling, for 3-unsubstituted pyrazolines 102 occur at position 3, yielding heterocycles 103 and in some cases as a mixture with 104 [108, 114, 115] (Scheme 2.26). This fact provides evidence for orbital control of these reactions. 

Aromatic compounds react mainly by electrophilic aromatic substitution, in which one or more ring hydrogens are replaced by various electrophiles. Typical reactions are chlorination, bromination, nitration, sulfonation, alkylation, and acylation (the last two are Friedel-Crafts reactions). The mechanism involves two steps addition of the electrophile to a ring carbon, to produce an intermediate benzenonium ion, followed by proton loss to again achieve the (now substituted) aromatic system. 

Know the meaning of electrophilic aromatic substitution, halogenation, nitration, sulfonation, alkylation, acylation, Friedel-Crafts reaction. 

Tables II to X give the melting points and, where applicable, the optical rotations of the inositols, inososes, inosamines, and quercitols, and of all of their known O-substituted derivatives. Anhydroinositols, although not substitution products in the strict sense, are included, as are the carbonyl-functional derivatives of the inososes. Halogen- and nitro-substituted cyclitols, and the C-methyl-inositols and their derivatives, are not included most of these compounds are referred to in the text. The derivatives are arranged in the following order salts (inosamines) or functional derivatives (inososes), carboxylic esters, borates, nitrates, sulfonic esters, phosphates, glycosides, acetals (and Schiff bases), ethers (and IV-alkyl derivatives), and anhydrides.

As with nitration, sulfonation proceeds only with difficulty due to cation formation. Knorr sulfonated 3-methylpyrazole in the 4-position by heating it at 100° for 6 hours in 20% oleum.208 Pyrazole sulfonic... 

Despite its V-excessive character , thiazole, just as with pyridine, is resistant to electrophilic substitution, the ring nitrogen atom deactivating the heterocyclic nucleus towards electrophilic attack. Moreover, most electrophilic substitutions which proceed in strongly acid media (nitration, sulfonation, Friedel-Crafts reactions) involve the protonated form... 

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