Silver nitrite, with alkyl halides

D. C. The mechanism of the reaction of silver nitrite with alkyl halides. The contrasting reactions of silver and alkali metal salts with alkyl halides. The alkylation of ambldent anions. J. Am. Chem. Soc.. 1955, 77, 6269-6280. 

The reaction of silver nitrite with secondary halides gives yields of nitroparaffins in the vicinity of 15%, while with tertiary halides the yields are even lower (0-5%). There is no question that the reaction of silver nitrite with alkyl halides is useful only for the synthesis of primary nitroparaffins. 

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... 

Aliphatic nitro compounds. These are isomeric with the alkyl nitrites and may be prepared from the alkyl halide and silver nitrite, for example C,H,aBr + AgNOj — C Hj NO + AgBr... 

Sodium nitrite can be used to form nitro compounds with primary or secondary alkyl bromides or iodides, though the method is of limited scope. Silver nitrite gives nitro compounds only when RX is a primary bromide or iodide. Nitrite esters are an important side product in all these cases (10-33) and become the major product (by an SnI mechanism) when secondary or tertiary halides are treated with silver nitrite. 

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. 

Primary alkyl iodides and bromides are excellent substrates for the Victor Meyer reaction, providing a route to both substituted and unsubstituted nitroalkanes (Table i. i).63,65,70,7i formation of the corresponding nitrite ester is a side-reaction and so the nitroalkane is usually isolated by distillation when possible. The reaction of primary alkyl chlorides with silver nitrite is too slow to be synthetically useful. Secondary alkyl halides and substrates with branching on... 

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

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. ... 

Alkyl halides are often used as substrates instead of alcohols. In such cases the salt of the inorganic acid is usually used and the mechanism is nucleophilic substitution at the carbon atom. An important example is the treatment of alkyl halides with silver nitrate to form alkyl nitrates. This is used as a test for alkyl halides. In some cases there is competition from the central atom. Thus nitrite ion is an ambident nucleophile that can give nitrites or nitro compounds (see 0-60).731 Dialkyl or aryl alkyl ethers can be cleaved with anhydrous sulfonic acids.732... 

Classically, primary nitroalkanes may be prepared by heating the alkyl bromide (or iodide) but not the chloride, with silver nitrite, frequently in anhydrous ether. The method is not satisfactory with secondary or tertiary halides, when the major products are the alkyl nitrites. 

This method is clearly expensive, and nowadays the cheaper sodium nitrite is employed with the alkyl halide in dimethyl sulphoxide or dimethylformamide as solvent.197 Although the yields are a little lower than in the silver nitrite method, a further feature is that secondary halides may be converted into secondary nitroalkanes, although even this modification fails with tertiary halides. The reaction is illustrated by the preparation of 2-nitrooctane (Expt 5.189). 

In experimental work indirect methods of introducing nitro groups find wide application as, for example, the substitution of a halogen (iodine or bromine in an alkyl iodide or bromide) by the Nitro group, by means of silver nitrite (the Victor Meyer reaction), and the new modification of this method described recently by Komblum et al. [4, 4a], in which alkyl halides are reacted with sodium nitrite. 

The interaction of alkyl halides with silver nitrite produces a mixture of the alkyl nitrite and the isomeric nitro compound in addition, alkyl nitrates may be formed. Straight-chain primary halides, preferably the bromides, give better yields than branched-chain primary, secondary, and tertiary halides. For the most part, the yields are low. In a similar manner, polynitroparaffins are obtained from polyhalides. 

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... 

Alkyl halides can be converted into nitro compounds by treatment with metal nitrites (for a review see Kornblum146). The older directions almost all prescribe silver nitrite at elevated temperatures (ca. 80-110°). However, because of the numerous side reactions it is only for the simplest primary iodides (up to about C5) that this reaction gives satisfactory yields (about 50%). Only in a few cases can bromides be used.643 Recently, however, the process has been made economic by using considerably milder conditions. It is advisable... 

Recently, however, Kornblum et al.651 showed that alkali nitrites, in particular sodium nitrite, can replace silver nitrite in the preparation of nitro compounds if dimethylformamide is used as solvent. The method has the additional advantage that not merely primary but also secondary alkyl iodides and bromides react readily in this solvent. Yields are around 60% in both cases. It usually suffices to stir the halide with an excess of sodium nitrite in dimethylformamide for some hours at room temperature primary iodides need about 2.5 hours, primary bromides about 6 hours for complete reaction. With secondary halides it is advisable to add urea as this raises the solubility... 

Another method for the aliphatic nitration is the reaction of alkyl halide with silver nitrite, in which considerable nitro compound is formed. With alkali nitrite on the other hand, very little nitro compound is formed. This difference... 

Another type of reaction may be mentioned here, which, while not oxidation-reduction, shows some of the possibilities in the way of relative oxidizing potentials of different atoms, or the relative aflSnities of the atoms for valence electrons. Silver nitrite ind sodiuiii nitrite when treated with an alkyl halide give different products. With the former, a nitro compound is obtained mainly with the latter a nitrite predominates. While according to the older views, this would point to different structures for the two nitrites, according to the principles developed in this book, the explanation of these differences involves tautomerism and several chemical equilibria. The reaction may be given in general terms as follows ... 

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