Nitration nitronium fluoroborate

A useful feature of this reagent is that high ratios of ortho to para products are found for some substituted aromatics. Finally, it possible to use nitronium-ion salts for nitration. Nitronium fluoroborate has been extensively studied. The trifluoromethanesulfonate salt is also readily prepared and is an active nitrating... 

From these results it appears that the 5-position of thiazole is two to three more reactive than the 4-position, that methylation in the 2-position enhances the rate of nitration by a factor of 15 in the 5-position and of 8 in the 4-position, that this last factor is 10 and 14 for 2-Et and 2-t-Bu groups, respectively. Asato (374) and Dou (375) arrived at the same figure for the orientation of the nitration of 2-methyl and 2-propylthiazole Asato used nitronium fluoroborate and the dinitrogen tetroxide-boron trifluoride complex at room temperature, and Dou used sulfonitric acid at 70°C (Table T54). About the same proportion of 4-and 5-isomers was obtained in the nitration of 2-methoxythiazole by Friedmann (376). Recently, Katritzky et al. (377) presented the first kinetic studies of electrophilic substitution in thiazoles the nitration of thiazoles and thiazolones (Table 1-55). The reaction was followed spec-trophotometrically and performed at different acidities by varying the... 

Chlorosulfonation of benzotrichloride with chlorosulfonic acid (28) or with sulfur trioxide (29) gives y -chlorosulfonyl benzoyl chloride [4052-92-0] in high yield. Nitration with nitronium fluoroborate in sulfolane gives 68% y -nitro-benzotrichloride [709-58-0] along with 13% of the ortho and 19% of the para isomers (30). 

The term macroscopic diffusion control has been used to describe processes in which the rate of reaction is determined essentially by the rate of mixing of the reactant solutions. The nitration of toluene in sulpholane by the addition of a solution of nitronium fluoroborate in sulpholane appears to fall into this class (Ridd, 1971a). Obviously, if a reaction is subject to microscopic diffusion control when the reactants meet in a homogeneous solution, it must also be subject to macroscopic diffusion control when preformed solutions of the same reactants are mixed. However, the converse is not true. The difficulty of obtaining complete mixing of solutions in very short time intervals implies that a reaction may still be subject to macroscopic diffusion control when the rate coefficient is considerably below that for reaction on encounter. The mathematical treatment and macroscopic diffusion control has been discussed by Rys (Ott and Rys, 1975 Rys, 1976), and has been further developed recently (Rys, 1977 Nabholtz et al, 1977 Nabholtz and Rys, 1977 Bourne et al., 1977). It will not be considered further in this chapter. 

Ostman122 has determined the kinetic isotope effect in the nitration of thiophene by benzoyl nitrate in acetonitrile the observed effect ( T/fcH= 1.14 + 0.10) is opposite to that expected for a primary isotope effect. It seems likely that it is a secondary a-isotope effect, ascribable to a rate-determining nature of the bond-formation step and similar to that observed by Olah et al. in the nitration of benzene derivatives with nitronium fluoroborate in tetramethylenesulfone.124... 

Whereas pyrazoles are quite readily iV-nitrated by nitric acid in acetic anhydride or with nitronium fluoroborate, imidazoles are usually far too basic, and give the nitrate salts instead. A nitro substituent, however, decreases the basicity sufficiently to allow iV-nitration to occur. The A -nitro compounds are subject to thermal rearrangement to the 2- and 4-nitro isomers, pointing to an alternative route to such compounds [63]. 

The nitrations are carried out under anhydrous conditions. This is of special advantage in dealing with compounds which under usual strong acidic nitration conditions may undergo hydrolysis or oxidation. Aryl nitriles, for example, are easily hydrolyzed under nitration conditions and no direct dinitration, requiring forceful conditions, was previously possible. The nitronium fluoroborate method enable us to carry out mono and dinitration of aryl nitriles with high yields without any hydrolysis of the -CN group. 

It has been mentioned ( 4.4.2) that nitronium tetraffuoroborate reaets with pyridine to give i-nitropyridinium tetraffuoroborate. This compound and several of its derivatives have been used to effect what is called the transfer nitration ofbenzeneandtoluene. i-Nitropyridinium tetraffuoroborate is only sparingly soluble in acetonitrile, but its homologues are quite soluble and ean be used without isolation from the solution in which they are prepared. i-Nitropyridinium tetra-fluoroborate did nitrate toluene in boiling aeetonitrile slowly, but not at 25 In eontrast, i-nitro-2-pieolinium tetraffuoroborate readily... 

Nitration, of o-aminobiphenyl to o-amiilo-/) -nitrobiphenyl, 46, 86 of o-tolunitrile with nitronium tetra-fluoroborate, 47, 56... 

Nitronium salts of the type NOa XQare very powerful nitrating agents. The counterion, X0, must be non-nucleophilic and usually is fluoroborate, BF4 or SbF 0 ... 

The nitration of 6-phenyl-2-pyridone (70% nitric acid or nitronium tetra-fluoroborate at RT) produces 3-nitro-6-phenyl-2-pyridone (up to 60% yield). However, nitration at 90°C with 70% nitric acid is reported to give 3-nitro-6-(4-nitrophenyl)-2-pyridone (36%), whereas at 90°C acetyl nitrate yields 50% of a mixture of 3- and 5-nitro-6-phenyl-2-pyridone (72KGS1374). 

Nitroimidazoles are readily made by nitration of imidazole or 1-substituted imidazoles in concentrated sulfuric acid (see Section 7.2.1). It is much more difficult to make 2-nitroimidazoles since direct nitration is seldom observed in the 2-position. Although electrophilic nitrodehalogenation reactions, too, occur mainly at C-4(5) [1], Katritzky has recently selectively nitrodeiodinated 2,4,5-triiodoimidazole to prepare 2,4(5)-dinitro-5(4)-iodo-and 2,4,5-triiiitroimidazoles, albeit in poor yield [2], Other routes to 2-nitroimidazoles include those which react a diazonium fluoroborate with the nitrite ion, and methods which oxidize 2-amino derivatives, themselves often only available by laborious sequences. The most appealing routes to 2-nitroimidazoles are the methods which make the 2-lithio derivative and treat it with a source of nitronium ion (e.g. n-propyl nitrate or N2O4) [3-5] (see Section 7.2.2). 

Use in a nitration A flask dried by flaming and cooled with a stream of nitrogen passing through it is charged with tetramethylene sulfone and nitronium tetra-fluoroborate and stirred at 10-20° during the addition of o-tolunitrilc. Eventually the temperature is raised and kept at 100-115° for 1 hr. 

No oxidation of alcohols is observed under the reaction conditions. The N-nitrocollidinium salt is generally less reactive than nitronium tetra-fluoroborate itself, but gives better control of conditions and superior yields as shown, for example, in the preparation of 1-adamantyl nitrate. Adamantanol gives less than 2% yield of nitrate ester upon treatment with nitronium tetrafluoroborate while the N-nitro salt forms the ester in 82 yield. 

Nitroxanthine is produced is produced as the major nitration product in reactions of 2 -deoxy-guanosine or ca//thymus DNA with nitryl chloride produced by mixing nitrite with hypochlorous acid, and 8-nitroguanidine was a minor product in these reactions (Chen et al. 2001). Formation of 8-nitroxanthine was also detected by xanthine reaction with various reactive nitrogen species, including nitryl chloride, peroxynitrite, nitronium tetra-fluoroborate, and heated nitric and nitrous acids. 

The use of mass spectrometry for identifying sulphated sugars is discussed in Chapter 21, and the nitration of nucleosides and nucleotides with nitronium tetra-fluoroborate is noted in Chapter 19. 

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