Nitration using nitronium tetrafluoroborate

Nitronium salts are efficient and powerful nitrating agents. Nitronium tetrafluoroborate is the most commonly used nitronium salt for nitration and is commercially available as a solid or as a solution in sulfolane in which the ions are highly solvated and exist as an ion pair. Nitronium tetrafluoroborate shows poor solubility in most organic solvents and so the more soluble nitronium hexafluorophosphate is sometimes preferred for nitrations. Olah and co-workers - have studied the nitration of a vast array of aromatics with nitronium salts. Solutions of nitronium salts in aprotic organic solvents are useful for the nitration of acid sensitive or readily oxidized substrates. Nitronium tetrafluoroborate has been used for the... 

Nitration of thiophene needs to be conducted in the absence of nitrous acid which can lead to an explosive reaction the use of acetyl nitrate or nitronium tetrafluoroborate are satisfactory. Invariably the major 2-nitro-product is accompanied by approximately 10% of the 3-isomer. Further nitration of either 2- or 3-nitrothiophenes" also leads to mixtures - equal amounts of 2,4- and 2,5-dinitrothiophenes from the 2-isomer, and mainly the former from 3-nitrothiophene. Similar, predictable isomer mixtures are produced in other nitrations of substituted thiophenes, for example 2-methylthiophene gives rise to 2-methyl-5- and 2-methyl-3-nitrothiophenes, and 3-methylthiophene gives 4-methyl-2-nitro- and 3-methyl-2-nitrothiophenes, " in each case in ratios of 4 1. 

A study of the nitration of xanthine and its iV-methyl derivatives has been carried out. In general 9-unsubstituted, and some 9-methyIxanthine, can be effectively nitrated with nitric acid in glacial acetic acid. However, 7-methylxanthine derivatives nitrate best using nitronium tetrafluoroborate [93JHC1221]. 

Pyridine itself can be converted into 3-nitropyridine only inefficiently by direct nitration even with vigorous conditions, however a pair of methyl groups facilitate electrophilic substitution sufficiently to allow nitration to compete with side-chain oxidation. Steric or/and inductive inhibition of A-nitration allows C-substitution using nitronium tetrafluoroborate, an example is 2,6-dichloropy-ridine dehalogenation of 2,6-dichloro-3-nitropyridine provides a practicable preparation of 3-nitropyridine. ... 

Another aminophthalide, 3-( -aminophenyl)-3-phenylphthalide [25], was synthesized from 3,3-diphenylphthalide. In this case, the starting material was mononitrated on one of the pendant groups by the use of acetyl nitrate or nitronium tetrafluoroborate. The resulting nitrophthalide was then reduced to the amine with hydrogen over Pt02 or with ammonium sulfide with overall yields of 85-90%. 

This salt turned out to be remarkably stable and a powerful, convenient nitrating agent for a wide variety of aromatics (and later also aliphatics). Over the years, this chemistry was further developed, and nitronium tetrafluoroborate is still a widely used commercially available nitrating agent. 

The selection of solvents for quantitative work is not easy. Nitro-alkanes are sufficiently inert, but nitronium tetrafluoroborate is poorly soluble in them c. 0-3 %). Nitronium salts react rapidly with acetic anhydride, and less rapidly with acetic acid, A, A -dimethylformamide and acetonitrile, although the latter solvent can be used for nitration at low temperatures. Sulpholan was selected as the most suitable solvent ... 

Quantitative eomparisons of aromatic reactivities were made by using the competitive method with solutions of nitronium tetrafluoroborate in sulpholan, and a concentration of aromatic compounds 10 times that of the salt. To achieve this condition considerable proportions of the aromatic compoimds were added to the medium, thus depriving the sulpholan of its role as true solvent thus, in the nitration of the alkyl- and halogeno-benzenes, the description of the experimental method shows that about 50-60 cm of mixed aromatic compounds were dissolved in a total of 130 cm of sulpholan. 

Salts containing the nitronium ion can be prepared and are reactive nitrating agents. The tetrafluoroborate salt has been used most frequently,8 but the... 

Nitration of acetylenes with nitryl iodide followed by elimination of HI gives nitroacetylenes, but nitroacetylenes are too thermally unstable to be useful for organic synthesis.77 Recently, nitro-trimethylsilyl-acetylenes are prepared as stable nitroacetylenes by the reaction of bis(trimethylsily)acetylene with nitronium tetrafluoroborate (Eq. 2.39).78... 

A large number of reagents are available for the preparation of nitro PAHs. These include fuming nitric acid in acetic acid (20) or acetic anhydride (13), sodium nitrate in trifluoroacetic acid (21) or trifluoroacetic acid and acetic anhydride (17), dinitrogen tetroxide in carbon tetrachloride (22), sodium nitrate in trimethyl phosphate and phosphorus pentoxide (23), and nitronium tetrafluoroborate in anhydrous acetonitrile (24). Alternative approaches must be used to synthesize nitro PAHs substituted at positions other than the most reactive carbon. For instance,... 

Olah and co-workers ° conducted a comprehensive study into the use of N-nitropyridinium salts for nitration. Such salts are easily prepared from the slow addition of the appropriate heterocyclic base to an equimolar suspension of nitronium tetrafluoroborate in acetonitrile. Olah studied the effect on nitration of changing both the structure of the heterocyclic base and the counter ion. Three of these salts (20, 21, 22) illustrated above have been synthesized and used for the 0-nitration of alcohols with success. Transfer nitrations with Al-nitropyridinium salts are particularly useful for the preparation of nitrate esters from acid-sensitive alcohols and polyols because conditions are essentially neutral. 

While nitramines are formed from the reaction of secondary amines with nitronium salts the success of the reaction depends on the basicity of the amine (Equation 5.11). Thus, amines of low to moderate basicity are A-nitrated in good yields. The nitration of more basic amines is slow and the nitrosamine is often observed as a significant by-product, a consequence of the partial reduction of the nitronium salt to the nitrosonium salt during the reaction. Increased reaction temperature is also found to increase the amount of nitrosamine formed. The amine substrate is usually used in excess to compensate for the release of the strong mineral acid formed during the reactions. Both nitronium tetrafluoroborate and the more soluble hexafluorophosphate are commonly used for A-nitrations. Solvents like acetonitrile, methylene chloride, nitromethane, dioxane, sulfolane, ethyl acetate and esters of phosphoric acid are commonly used. 

Olsen and co-workers used a solution of nitronium tetrafluoroborate in acetonitrile for the V-nitration of acetamides and urethanes at —30°C. The following nitramides were obtained by this method V-nitroacetamide (13 %), V-nitro-2-chloroacetamide (55 %), V-nitro-n-butylacetamide (40 %), V-nitrobenzamide (53 %), ethyl V-nitro-n-butylcarbamate (91 %) and V-nitrosuccinimide (43 %). The low yield of V-nitroacetamide, a primary nitramide, is attributed to competing hydrolysis due to the release of tetrafluoroboric acid as the reaction progresses. The scope of the reaction is improved by moving to more basic solvents like ethyl acetate, 1,4-dioxane and trimethyl phosphate. ... 

Ammonium dinitramide (152) is synthesized by treating a solution of ammonium ni-trourethane (150) with nitronium tetrafluoroborate or dinitrogen pentoxide in methylene chloride at -30 °C, followed by ammonolysis of the resulting ethyl A,lV-dinitrourethane (151)7 Ammonium dinitramide can be prepared from the nitration of ethyl carbamate and ammonium carbamate with the same reagents. This is currently the most efficient route to ammonium dinitramide and is used for its manufacture (Section 9.11). 

Alkyl lV,lV-dinitramines (154) have been prepared from the reaction of the tetraalkylam-monium salts (155) of primary nitramines with nitryl fluoride in acetonitrile at subambient temperature. The same reaction with the primary nitramine or its alkali metal salts yields the corresponding nitrate ester. Treatment of the ammonium, potassium, or lithium salts of primary nitramines (156) with a solution of nitronium tetrafluoroborate in acetonitrile at subambient temperature yield alkyl iV,iV-dinitramines. ° The same reactions in ether or ester solvents enables the free nitramine to be used. The nitrolysis of A-alkylnitramides (157) and N,N-diacylamines with nitronium tetrafluoroborate in acetonitrile, and the nitration of aliphatic isocyanates with nitronium tetrafluoroborate and nitric acid in acetonitrile, also yield alkyl A,A-dinitramines (154). 

Nitronium tetrafluoroborate used in large excess (>6 equiv.) is able to transform hexamethylbenzene and its derivatives to dinitroprehnitene (1,2,3,4-tetramethyl-5,6-dinitrobenzene) in a highly selective nitration process486 [Eq. (5.180)]. Scheme 5.47 summarizes the key steps of the mechanistic proposal, including the ipso - n i tro are n iu m ion 123, the formation of benzyl nitrite 124, and the complexation of the N02+ ion to form the mononitro intermediate (125) facilitating the attack to the ortho position resulting in the formation of the 1,2-dinitro product. 

Nitropyrazoles are formed exclusively in the case of nitration using nitric acid in acetic anhydride and nitronium tetrafluoroborate in sulfolane. 

This reaction has been further investigated [80JCS(P2)773] and the products have been confirmed as being, with nitric acid alone, 44d,e, and f, whereas mixed acid (and nitronium tetrafluoroborate) gives mainly 3-nitrophenyl products, viz.44b,c, and e. The nitration of the mononitrophenyl-1,3,4-oxadiazoles shows considerable variation of product ratios according to the conditions used. 

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