Preparation of Nitroalkanes

Nitromethane is a highly desired product which has many uses. It is a known preservative for chlorinated hydrocarbons, a fuel additive and an intermediate compound in the formation of various other chemicals, such as chlorpicrin. Nitromethane is the most commercially desired compound of the nitroparaffins. 

A stainless steel reaction vessel of 10 cc volume was charged with 0.56 part sodium nitrite, 0.8 part of distilled water and 0.34 part sodium bicarbonate. The vessel was cooled with liquid nitrogen under a blanket of argon to assure lack of air moisture condensation in the vessel. To the chilled vessel was added 3.9 parts of liquid methyl chloride (measured and weighed at—77° C. with density taken at 1.1). 3.5 parts of the added methyl chloride was excess over that required for stoichiometry. The vessel was sealed and heated at 75° C. for 4 hours with agitation. The resultant material was analyzed by conventional gas chromatographic analysis and showed that nitromethane was obtained in 57 percent yield. The selectivity to nitromethane was 74 percent based on the sodium nitrite. 

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The reaction of alkyl halides with metal nitrites is one of the most important methods for the preparation of nitroalkanes. As a metal nitrite, silver nitrite (Victor-Meyer reaction), potassium nitrite, or sodium nitrite (Kornblum reaction) have been frequently used. The products are usually a mixture of nitroalkanes and alkyl nitrites, which are readily separated by distillation (Eq. 2.47). The synthesis of nitro compounds by this process is well documented in the reviews, and some typical cases are listed in Table 2.3.92a Primary and secondary alkyl iodides and bromides as well as sulfonate esters give the corresponding nitro compounds in 50-70% yields on treatment with NaN02 in DMF or DMSO. Some of them are described precisely in vol 4 of Organic Synthesis. For example, 1,4-dinitrobutane is prepared in 41 -46% yield by the reaction of 1,4-diiodobutane with silver nitrite in diethyl ether.92b 1-Nitrooctane is prepared by the reaction with silver nitrite in 75-80% yield. The reaction of silver nitrite with secondary halides gives yields of nitroalkanes of about 15%, whereas with tertiary halides the yields are 0-5%.92c Ethyl a-nitrobutyrate is prepared by the reaction of ethyl a-bromobutyrate in 68-75% yield with sodium nitrite in DMF.92d Sodium nitrite is considerably more soluble in DMSO than in DMF as a consequence, with DMSO, much more concentrated solutions can be employed and this makes shorter reaction times possible.926... 

The Michael addition reaction is commonly recognized as one of the most important carbon-carbon bond-forming reactions in organic synthesis, and major efforts have been made to develop efficient catalytic systems for this type of transformation. In particular, the Michael addition of a carbon nucleophile to nitroalkenes is a useful synthetic method for the preparation of nitroalkanes [76], which are versatile synthetic intermediates owing to the various possible easy transformations of the nitro group into other useful functional groups, such as amino groups and nitrile oxides. 

Ozonation of Heteroatoms. Phosphines are converted to phosphine oxides and phosphites to phosphates by ozone. These reactions are quite general and a wide range of sub-stitutents can be tolerated. Phosphine oxides also can be produced by the ozonation of alkylidenetriphenylphosphoranes or of thio- or selenophosphoranes. Organic sulfides are converted to sulfoxides and sulfones by ozonation. Tertiary amines are converted to amine oxides, while nitro compounds can be produced in modest yields by ozonation of primary amines. This preparation of nitroalkanes compares well with alternate approaches using peroxides, peroxy acids, permanganate, or Monoperoxysulfuric Acid, but ozonation on silica gel has proven to be superior (see Ozone-Silica Get). Selenides are converted to selenoxides by ozone and this reaction is often used to achieve overall production of unsaturated carbonyl compounds. An example is shown in eq 25. ... 

Conjugate reductions of nitroolefins have also been widely studied and a wide range of reagents are available for the preparation of nitroalkanes and various other compounds (vide infra) from... 

Table 9.6. Preparation of nitroalkanes from alkali metal nitrites under phase transfer conditions...

Hydroxylamine can be prepared by a variety of reactions involving the reduction of nitrites, nitric acid or NO, or by the acid hydrolysis of nitroalkanes. In the conventional Raschig synthesis, an aqueous solution of NH4NO2 is reduced with HS04 /S02 at 0° to give the hydroxylamido-A ,A -disulfate anion which is then hydrolysed stepwise to hydroxylammonium sulfate ... 

The Michael addition of nih oalkanes to alkenes substituted with two elecbon-withdrawing groups at the a- and 3-positions provides a new method for the preparation of functionalized alkenes. Although reactions are not new, Ballini and coworkers have used this sbategy in the synthesis of polyfunctionalized unsaturated carbonyl derivatives by Michael addition of nih oalkanes to enediones as shown in Eqs. 7.124-7.126. Success of this type of reaction depends on the base and solvent. They have found that DBU in acetonihile is the method of choice for this puipose. This base-solvent system has been used widely in Michael additions of nitroalkanes to elechon-deficient alkenes (see Section 4.3, which discusses the Michael addition). ... 

Nitrodesilylation (Eq. 2.17)36 and nitrodestanylation (Eq. 2.18)37 are efficient methods for the preparation of some kinds of nitroalkanes from readily available alkylsilanes or allylstan-nanes. Similar nitration also takes place at the vinylic positions (see Eq. 2.36 in Section 2.1.4). 

Nitromethylation of aldehydes has been carried out in a one pot procedure consisting of the Henry reaction, acetylation, and reduction with sodium borohydride, which provides a good method for the preparation of l-nitroalkanes.16b 79 It has been improved by several modifications. The initial condensation reaction is accelerated by use of KF and 18-crown-6 in isopropanol. Acetylation is effected with acetic anhydride at 25 °C and 4-dimethylaminopyridine (DMAP) as a catalyst. These mild conditions are compatible with various functional groups which are often... 

The addition of alkoxides to 2-nitro-l-phenylthio-l-alkenes affords P-nitro-aldehyde acetals.276 The reaction of the same nitroalkenes with amines gives nitroenamines.270 They are important intermediates for organic synthesis and are generally prepared by the reaction of nitroalkanes with triethylorthoformate in the presence of alcohols or secondary amines.2"1 0 The methods of Eqs. 4.20 and 4.21 have some merits over the conventional methods, for variously substituted (3-nitro-aldehydes acetals or nitroenamines are readily prepared by these methods. 

An alternative method for the stereoselective preparation of 1,2-diamines is shown in Eq. 4.29, in which the addition of nitroalkanes to imines is used as a key reaction.35... 

The Michael addition of nitro compounds is a useful method for the preparation of various natural products. The Michael addition of nitroalkanes to dehydroalanines gives y-nitro-a-amino acids, which provides a convenient synthesis of side-chain modified a-amino acids (Eq. 4.114).152 Transformations of y-nitro-a-amino acid derivatives into a-amino acids occur by reductive denitration (see Section 7.2) into y-oxygenated a-amino acids by the Nef reaction (Eq. 

The Michael addition of nitroalkanes to a,P-unsaturated ketones followed by the Nef reaction has been extensively used as a method for the conjugated addition of acyl anions to enones (see Section 6.1, Nef Reaction). This strategy is one of the best methods for the preparation of 1,4-dicarbonyl compounds.156a h Various natural products have been prepared via this route.157 For example, r/.v-jasmone is prepared from readily available materials, as shown in Scheme 4.19.156f... 

The synthesis of 2,3,5-trialkylpyrroles can be easily achieved by conjugate addition of nitroalkanes to 2-alken-l,4-dione (prepared by oxidative cleavage of 2,5-dialkylfuran) with DBU in acetonitrile, followed by chemoselective hydrogenation (10% Pd/C as catalyst) of the C-C- double bond of the enones obtained by elimination of HN02 from the Michael adduct. The Paal-Knorr reaction (Chapter 10) gives 2,3,5-trialkylpyrroles (Eq. 4.124).171... 

The carboxylation of nitroalkanes with magnesium methyl carbonate followed by esterification gives a-nitro esters in 40-58% yield.14 Magnesium methyl carbonate is prepared by the saturation of a magnesium methoxide suspension in DMF with C02. More elegantly, sodium salt of nitroalkanes can he carboxylated by means of 1 -ethoxycarbonylbenzotriazole to give a-nitro esters in 55-80% yield (Eq. 5.7).15 Nitroacetic acids and its esters can serve as useful... 

In a similar way, a-nitroselenides are prepared via the reaction of nitronates with phenylse-lenyl bromide, which gives a new synthetic method of l-nitroalkenes from nitroalkanes.130 The sequence of a-selenation, nitro-aldol reaction, and oxidation provides a useful method for the preparation of nitroalkenes with a hydroxymethyl group (Eq. 5.81).131... 

Various a-nitronitriles are readily prepared by the reaction of Eq. 7.7 the reaction of a-nitronitriles with nitroalkane salts provides an excellent method for the preparation of P-nitronitriles (Eq. 7.9).7... 

The Henry reaction of nitroalkanes followed by denitration is a good method for the preparation of alcohols. This methodology has been applied in carbohydrate chemistry. For... 

The Michael addition of nitroalkanes followed by denitration is also a useful method for the preparation of C-disaccharide. The Michael addition of glucosyl nitromethane to the levoglu-cosenone proceeds stereoselectively, and subsequent denitration gives the C-disaccharide in... 

Because the a-nitroketones are prepared by the acylation of nitroalkanes (see Section 5.2), by the oxidation of (3-nitro alcohols (Section 3.2.3), or by the nitration of enol acetates (Section 2.2.5), denitration of a-nitro ketones provides a useful method for the preparation of ketones (Scheme 7.10). A simple synthesis of cyclopentenone derivatives is shown in Eq. 7.66.76... 

A series of 3-substituted-2-isoxazoles are prepared by the following simple procedure in situ conversion of nitroalkane to the silyl nitronate is followed by 1,3-dipolar cycloaddition to produce the adduct, which undergoes thermal elimination during distillation to furnish the isoxazole (Eq. 8.74). 5 Isoxazoles are useful synthetic intermediates (discussed in the chapter on nitrile oxides Section 8.2.2). Furthermore, the nucleophilic addition to the C=N bond leads to new heterocyclic systems. For example, the addition of diallyl zinc to 5-aryl-4,5-dihydroi-soxazole occurs with high diastereoselectivity (Eq. 8.75).126 Numerous synthetic applications of 1,3-dipolar cycloaddition of nitronates are summarized in work by Torssell and coworker.63a... 

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