Nitro compounds, reaction with halides

A mechanism of this type permits substitution of certain aromatic and ahphatic nitro compounds by a variety of nucleophiles. These reactions were discovered as the result of efforts to explain the mechanistic basis for high-yield carbon alkylation of the 2-nitropropane anion by p-nitrobenzyl chloride. p-Nitrobenzyl bromide and iodide and benzyl halides that do not contain a nitro substituent give mainly the unstable oxygen alkylation product with this ambident anion ... 

The most common types of aryl halides in nucleophilic aromatic substitutions are those that bear- o- or p-nitro substituents. Among other classes of reactive aryl halides, a few merit special consideration. One class includes highly fluorinated aromatic compounds such as hexafluorobenzene, which undergoes substitution of one of its fluorines on reaction with nucleophiles such as sodium methoxide. 

Such cyclohexadienes are easily oxidizable to benzenes (often by atmospheric oxygen), so this reaction becomes a method of alkylating and arylating suitably substituted (usually hindered) aryl ketones. A similar reaction has been reported for aromatic nitro compounds where 1,3,5-trinitrobenzene reacts with excess methyl-magnesium halide to give 2,4,6-trinitro-l,3,5-trimethylcyclohexane. Both... 

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 carbon-carbon bond forming reactions of nitro compounds by alkylation with alkyl halides or acylation with acyl halides have been encountered with difficulties of the competing O-alkylation or O-acylation, respectively. In this chapter, the recent developments of C-alkylations and C-acylations of nitro compounds are summarized. The O-alkylated compounds undergo cycloaddition reactions, which are discussed in the chapter of cycloaddition (Chapter 8). 

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. 

The first demonstration of fluorous synthesis was in the preparation of small (8-12 members) isoxazo-line and isoxazole libraries by the three-step procedure outlined in Figure 8.1461 All reactions were purified by three-phase liquid-liquid extraction. The starting substrates were simple allylic alcohols which were tagged with the fluorous silyl halide 5 to make substrates 6 for an ensuing dipolar cycloaddition. This was conducted by the Mukaiyama method with a large excess of nitro compound and... 

One of the most important reactions for the laboratory synthesis of primary aliphatic nitro compounds was discovered by V. Meyer and O. Stiiber in 1872 and involves treating alkyl halides with a suspension of silver nitrite in anhydrous diethyl ether. Benzene, hexane and petroleum ether have also been used as solvents for these reactions which are usually conducted between 0 °C and room temperature in the absence of light. 

The synthesis of aliphatic nitro compounds from the reaction of alkyl halides with alkali metal nitrites was discovered by Kornblum and co-workers and is known as the modified Victor Meyer reaction or the Kornblum modification. The choice of solvent in these reactions is crucial when sodium nitrite is used as the nitrite soiuce. Both alkyl halide and nitrite anion must be in solution to react, and the higher the concentration of nitrite anion, the faster the reaction. For this reason, both DMF and DMSO are widely used as solvents, with both able to dissolve appreciable amounts of sodium nitrite. Although sodium nitrite is more soluble in DMSO than DMF the former can react with some halide substrates.Urea is occasionally added to DMF solutions of sodium nitrite to increase the solubility of this salt and hence increase reaction rates. Other alkali metal nitrites can be used in these reactions, like lithium nitrite,which is more soluble in DMF than sodium nitrite but is also less widely available. 

Silver nitrite gives significantly higher yields of nitro compounds from primary alkyl halides, and consequently, the synthesis of Q, ty-dinitroalkanes from the reaction of o, )-dihaloalkanes with sodium nitrite is inferior to the same reaction with silver nitrite (Table 1.2). However, the use of a solvent system composed of DMSO and MEK is reported to considerably improve the yields of Q , y-dinitroalkane when using sodium nitrite. ... 

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