Secondary nitroalkane

Secondary nitroalkanes also give silylnitronates, however, in decreased yields (30 40%)24. Due to their lower stability compared to silylnitronates derived from primary nitroalkanes. they arc prepared as tm-butyldirnethylsilyl derivatives. 

In the presence of a catalytic amount of tetrabutylammonium fluoride, either freshly dried over molecular sieves22 or as the trihydrate16, silylnitronates 2 derived from primary nitroalkanes react readily at — 78 C or below, via their in situ generated nitronates. with aromatic and aliphatic aldehydes to give the silyl-protected (/J, S )-nitroaldol adducts 3 in excellent yield4,22-24-26,27. Silylnitronates, derived from secondary nitroalkanes. afford the adducts in 30 40% overall yield24. In contrast to the classical Henry reaction (vide supra), the addition of silylnitronates to aldehydes is irreversible. Ketones are unreaetive under such conditions. 

Whereas secondary nitroalkanes such as 1-nitrocyclohexane 1766 are reduced to the corresponding oximes, for example 1767 [24], primary nitro compounds such as a-nitro-o-xylene 1768 or unsaturated nitro compounds such as 1770 are transformed into nitriles such as 1769 and 1771 [24] (Scheme 12.6). 

Conway, C.C., Nie, G., Huesain, N.S. and Fiala, E.S. (1991). Comparison of otddative damage to rat liver DNA and RNA by primary nitroalkanes, secondary nitroalkanes, cyclo-pentanone oxime and related compounds. Cancer Res. 51, 3143-3147. 

Successive treatment of primary or secondary nitroalkanes with triethylamine and hex-adecyltrimethylammonium permanganate affords aldehydes or ketones, respectively (e.g. equation 129). Hydroxyl groups and olefinic double bonds are not affected421. 

Selected examples of the Michael-type addition of secondary nitroalkanes with electron-deficient alkynes... 

Secondary nitroalkanes are oxidized by cetyltrimethylammonium permanganate to yield ketones in moderate to good yield [44]. The reaction is sufficiently mild to leave double bonds and hydroxyl groups unaffected. 

Conversion of a primary or secondary nitroalkane into the corresponding carbonyl compound. 

Primary nitroalkane Secondary nitroalkane Tertiary nitroalkane... 

Aliphatic nitroalkanes can be categorized into six basic groups primary, secondary and tertiary nitroalkanes, terminal and internal gem-dinitroalkanes, and trinitromethyl compounds. Primary and secondary nitroalkanes, and terminal gem-dinitroalkanes, have acidic protons and find particular use in condensation reactions for the synthesis of more complex and... 

Olsen and co-workers reported the nitration of secondary nitroalkanes to m-dinitro compounds with nitronium tetrafluoroborate in acetonitrile at 0 °C. Yields are lower compared to the Kaplan-Shechter reaction and significant amounts of pseudonitroles are formed, but this is possibly due to impure reagent. 

The tautomeric nitronic acids of secondary nitroalkanes or their nitronate salts react with nitrous acid or alkali metal nitrites to yield pseudonitroles.These pseudonitroles are often isolated as their colourless dimers (78b) but are deep blue in monomeric form (78a). Primary nitroalkanes also form pseudonitroles (80b) but these rapidly isomerise to the nitrolic acid (80a).Reactions are commonly conducted by slowly acidifying a mixture containing the nitronate salt and the metal nitrite, during which, the nitronic acid reacts with the nitrite anion. These reactions, first discovered by Meyer, have been used to prepare 2-nitroso-2-nitropropane (78a) and acetonitrolic acid (80a) from 2-nitropropane (76) and nitroethane (22) respectively. ... 

Oxidative nitration, a process discovered by Kaplan and Shechter, is probably the most efficient and useful method available for the synthesis of em-dinitroaliphatic compounds from the corresponding nitroalkanes. The process, which is an electron-transfer substitution at saturated carbon, involves treatment of the nitronate salts of primary or secondary nitroalkanes with silver nitrate and an inorganic nitrite in neutral or alkali media. The reaction is believed ° °° to proceed through the addition complex (82) which collapses and leads to oxidative addition of nitrite anion to the nitronate and reduction of silver from Ag+ to Ag . Reactions proceed rapidly in homogeneous solution between 0 and 30 °C. 

A range of primary and secondary nitroalkanes and their derivatives have been converted to the corresponding gem-dinitroalkanes via oxidative nitration, including the conversion of nitroethane, 1-nitropropane, 2-nitropropane and 2-nitro-1,3-propanediol to 1,1-dinitroethane (78 %), 1,1-dinitropropane (86 %), 2,2-dinitropropane (93 %) and 2,2-dinitro-1,3-propanediol (77 %) respectively. The silver nitrate used in these reactions can be recovered quantitatively on a laboratory scale and this has led to a study where oxidative nitration has been considered for the large-scale production of 2,2-dinitropropanol (25) from the nitroethane (22). ... 

Kaplan and Shechter found that certain oxidants react with the nitronate salts of secondary nitroalkanes to yield vic-dinitroalkanes (111) in a reaction referred to as oxidative dimerization. These reactions are believed to involve transfer of an electron from the secondary alkyl nitronate to the oxidant with the production of a nitroalkyl radical. The radical can then dimerize to the corresponding vtc-dinitroalkane (111) (Equation 1.2) or lose nitric oxide to form a ketone via the Nef reaction (Equation 1.3). Unfortunately, formation of the ketone is a major side-reaction during oxidative dimerization and is often the major product. 

Primary and secondary nitroalkanes, and substrates containing terminal em-dinitroaliphatic functionality, have one or more acidic a-protons, a consequence of inductive and resonance effects imposed by the nitro group. As a result, such compounds can behave like carbanions and participate in a number of addition and condensation reactions which are typical of substrates like ketones, aldehydes, and /S-ketoesters. Such reactions are extremely useful for the synthesis of functionalized polynitroaliphatic compounds which find potential use as explosives, energetic oligomers and plasticizers. 

Dinitromethane has two acidic protons and reacts with Michael acceptors to form bis-adducts. " Secondary nitroalkanes can only react with one equivalent of Michael acceptor. In the absence of steric effects primary nitroalkanes usually react with two equivalents of Michael acceptor to form bis-adducts. Depending on the reaction stoichiometry, 1,4-dinitrobutane can be reacted with methyl acrylate to form either the bis-adduct (129) or the tetra-adduct (130) in good yield. " ... 

Primary and secondary nitroalkanes, dinitromethane, and terminal em-dinitroaliphatic compounds like 1,1-dinitroethane, all contain acidic protons and have been used to generate Mannich products. Formaldehyde is commonly used in these reactions although the use of other aliphatic aldehydes has been reported. The nitroalkane component is frequently generated in situ from its methylol derivative, a reaction which also generates formaldehyde. Ammonia, " aliphatic amines, " hydrazine, and even urea have been used as the amine component of Mannich reactions. 

Bowman and co-workers synthesized 2-azido-2-nitropropane by treating the sodium salt of 2-nitropropane with a mixture of sodium azide and potassium ferricyanide. Olah and co-workers used the same methodology for the synthesis of alicyclic gem-azidonitroalkanes from secondary nitroalkanes. Isomeric azidonitronorbornanes (38) and (39) were synthesized from 2,5-dinitronorbornane (37). Some of the gem-azidonitroalkanes synthesized during this work have poor chemical and thermal stability. 

Aliphatic nitro compounds with the nitro group on a tertiary carbon were reduced to amines with aluminum amalgam [146 or iron [559]. 2-Nitro-2-methylpropane afforded ferf-butylamine in 65-75% yield [146. Even some secondary nitroalkanes were hydrogenated to amines. fra s-l,4-Dinitrocy-clohexane was converted to frans-l,4-diaminocyclohexane with retention of configuration. This may be considered as an evidence that the intermediate nitroso compound is reduced directly and not after tautomerization to the isonitroso compound [560] (see Scheme 54). 

A more common method for the preparation of silyl nitronates is the use of trimethylsilyl chloride (TMSCl) in the presence of a base. With triethylamine, silyl nitronates are prepared from primary nitroalkanes in moderate yields however, it is necessary to conduct the silylation in acetonitrile for good yields with secondary nitroalkanes (18,101). In several cases, this silylation has been done in the presence of the dipolarophile for both inter- and intramolecular processes, or the nitronate has been used in subsequent reactions without purification (18,22). Employment of l,8-diazabicyclo(5.4.0)undec-7-ene (DBU) as the base allows this procedure to be general for most nitroalkanes (19). 

There are also several variations on this procedure. The use of trimethylsilyl triflate (TMSOTQ provides the silyl nitronate of methyl nitroacetate in good yield. However, for primary nitroalkanes, a second silylation occurs at the a-position of the nitronate (Eq. 2.5) (102). The use of TMSCl in the presence of lithium sulfide provides good yields of silyl nitronates from secondary nitroalkanes (103,104). Unfortunately, the number of examples is limited and this procedure is not applicable to primary nitroalkanes. 

The nitronates derived from secondary nitroalkanes suffer from greatly decreased reactivity (Table 2.33). The reaction of the silyl nitronate of methyl nitromalonate with methyl acrylate proceeds in 96 h at room temperamre (entry 1), while the corresponding monosubstituted nitronate (85) proceeds in 1 h (entry 5, Table 2.32) (16). Nitronates with dialkyl substitution typically require elevated temperatures for complete reaction (101). For example, the silyl nitronate of 2-nitropropane and nitrocyclopentane both react in under 3 h at 50 °C in acetonitrile... 

Secondary nitroalkanes react with primary amines to give imines [53]. 

Nitroalkanes (Tables 12 and 13) These are possibly among the most useful substrates for reaction with the superoxide/dioxygen reagent, and the loss of nitrite, according to Scheme 21, has been confirmed. Secondary nitroalkanes are efficiently converted into ketones (Table 12), and the reaction may prove to be of especial value for the preparation of 1,4-diketones. 

Fiala, E.S., Sodum, R.S., Hussain, N.S., Rivenson, A. Dolan, L. (1995) Secondary nitroalkanes induction of DNA repair in rat hepatocytes, activation by aryl sulfotransferase and hepatocarcinogenicity of 2-nitrobutane and 3-nitropentane in male F344 rats. Toxicology, 99, 89-97... 

The oxidative hydrolysis of nitronate salts from secondary nitroalkanes (see Expt 5.84). 

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