Nitroalkanes from alkyl halides

Table 2.3 Synthesis of nitroalkanes from alkyl halides...

Thus, the direct alkylation of the anions derived from nitroalkanes with alkyl halides has some difficulties, and such difficulties are partially overcome by the radical reaction or transition metal catalyzed reactions, as discussed in Sections 5.4 and 5.5. 

X" = NOj- From Amberlyst A-26 or Amberlite IRA 400 From Amberlite IRA 900 (C1-) by treatment with NaNO, soln. 3 Synthesis of nitroalkanes and alkyl nitrites from alkyl halides. - a-Nitro carboxylic esters from a-bromo esters alkyl-nitro compounds from primary, secondary and benzylic bromides (formation of nitrites was not detected). ... 

Alkyl mercury halides participate in a photo-sdmidated rathcM chain reacdon of the anion of nitroalkanes Isee Eq. 5.38 in which a 375-W sun lamp Is used." Primary, secondary, and ternary alkyl rathcMs generated from alkyl mercury halides react with the anion of ttitroalkanes to form new C-C bonds. 

Monoanions derived from nitroalkanes are more prone to alkylate on oxygen rather than on carbon in reactions with alkyl halides, as discussed in Section 5.1. Methods to circumvent O-alkylation of nitro compounds are presented in Sections 5.1 and 5.4, in which alkylation of the a.a-dianions of primary nitro compounds and radial reactions are described. Palladium-catalyzed alkylation of nitro compounds offers another useful method for C-alkylation of nitro compounds. Tsuj i and Trost have developed the carbon-carbon bond forming reactions using 7t-allyl Pd complexes. Various nucleophiles such as the anions derived from diethyl malonate or ethyl acetoacetate are employed for this transformation, as shown in Scheme 5.7. This process is now one of the most important tools for synthesis of complex compounds.6811-1 Nitro compounds can participate in palladium-catalyzed alkylation, both as alkylating agents (see Section 7.1.2) and nucleophiles. This section summarizes the C-alkylation of nitro compounds using transition metals. 

Synthesis of nitroalkanes and their derivatives from the reaction of alkyl halides with silver nitrite under the Victor Meyer conditions... 

The reaction of a -halocarboxylic acids with sodium nitrite has been used to synthesize ni-tromethane, nitroethane and nitropropane, although the reaction fails for higher nitroalkanes. " A number of other reactions have been reported which use nitrite anion as a nucleophile, including (1) reaction of alkyl halides with potassium nitrite in the presence of 18-crown-6, (2) reaction of alkyl halides with nitrite anion bound to amberlite resins, (3) synthesis of 2-nitroethanol from the acid-catalyzed ring opening of ethylene oxide with sodium nitrite, and (4) reaction of primary alkyl chlorides with sodium nitrite in the presence of sodium iodide. ... 

Surprisingly few simple nitroalkanes are commercially available but more complex examples can be prepared readily by alkylation of the anions derived from nitromethane, nitroethane, and 2-nitro-propane. Deprotonation of nitroalkanes with butyllithium followed by the addition of alkyl halides gives the alkylated nitroalkanes in good yield. Some examples of this general method are shown below. These reactions really do have to be done in two steps BuLi is not compatible with alkyl halides ... 

Caldarelli et al. (240) have recently reported a five-step synthesis of substituted p)Trole libraries L22 and L23 using solid-supported reagents and scavengers. The synthesis involved oxidation of benzyl alcohols Mi to aldehydes (step a, Fig. 8.46), Henry reaction of aldehydes 8.91 with nitroalkanes M2 (step b), and acylation and elimination of nitroalcohols 8.93 (steps c and d) to give the nitrostyrenes 8.94, which were subjected to 1,3-dipolar cycloaddition with an isocyanoacetate (step e) to give the pyrroles 8.95. N-alkylation of these pyrroles with alkyl halides (step f) and final library-from-a-library hydrolysis/decarboxylation of L22 gave a library of trisub-stituted pyrroles L23 (step g. Fig. 8.46). 

Reaction of alkyl halides with sodium nitrite Nitromercuralion of alkcncs Formation of nitroalkanes from nitrate esters Chemical properiics of nitroalkanes Nitronic acids... 

It will be recalled that methane (CH4) can be converted to nitromethane (H3CNO2) by the action of nitric acid on methane at high temperature (Chapter 6, Equation 6.10). The nitration of other alkanes by the same process can also be effected, but separation of the multitude of isomers that can be formed (from all but the simplest alkanes) can be difficult. Nitroalkanes, R-NO2 (sometimes accompanied by their corresponding nitrite isomers, R-ONO), can also be prepared (as shown in Chapter 7, Table 7.5e) by treatment of alkyl halides with nitrite anion (ONO ). Reduction of nitroalkanes (R-NO2) with hydrogen (H2) in the presence of a platinum (Pt) catalyst or lithium aluminum hydride (LiAIlT,) in ether produces the corresponding amine (Equation 10.18). 

Among other reactions, the bis-metallated species (151) derived from nitroalkanes condense with dialkyl carbonates to give comp>ounds (152), in 60—80% yield, which can serve as precursors of both a-amino-acids and a-hydroxyamino-esters as well as a-keto-esters. Oxazolin-5-ones (153) can be alkylated at the 4-position by alkyl halides in hot DMF containing HMPA and ethyldi-isopropylamine. Yields are good (60—90%) for allylic, benzylic, and propargylic halides but otherwise poor (e.g. 32% with EtI) under these conditions acid hydrolysis of the products affords substituted a-amino-acids. Mesoionic l,3-oxazol-5-ones (154), obtained from imidoyl chlorides and acyl-tetracarbonylferrates, react with alcohols to give N-acyl-a-amino-acid esters. ... 

Victor Meyer refluxed amyl iodide with silver nitrite and obtained a mixture of the alkyl nitrite and nitroalkane. By improved procedures " it is possible to obtait pure nitroparafiins from primary straight-chain halides in high yield. An example U the preparation of 1-nitrooctane." 1-Bromooctane is added in 2 hrs. with stirring... 

Alkylation solves the awkward problem of how to make aryl ketones of the pattern 151, awkward because the Friedel-Crafts reaction doesn t work with this substitution pattern. Alkylation of a nitroalkane with the benzylic halide 149 does work well and the product 150 can be oxidised to the ketone32151. Reactions with aldehydes work even with masked aldehydes33 like dihydropyran to give 154 and hence the ketone 155 with a 1,2-substitution pattern after hydrolysis.34 More vigorous conditions give nitroalkenes 145 from aldehydes and these will be very useful later as a2 reagents. 

For example, tertiary p-nitrocumyl halides can act as alkylating agents in high yield. The nucleophile need not be a nitroalkane anion, but can be such anions as thiolate, phenolate, or a carbanion such as those derived from malonate esters. The same... 

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