Nitroalkanes dimerization

Aliphatic primary amines are known to be oxidized by dimethyl dioxiranes to various products such as oximes, nitroso dimers, nitroalkanes, nitrones and oxazrridines under various conditions depending upon the oxidation reaction . In contrast, when secondary amines lacking a-hydrogens are allowed to react with Oxone and PTC in buffered acetone solution at 0 °C, nitroxides are obtained in good yields in a few minutes (equation 61) . 

The most characteristic reaction of butadiene catalyzed by palladium catalysts is the dimerization with incorporation of various nucleophiles [Eq. (11)]. The main product of this telomerization reaction is the 8-substituted 1,6-octadiene, 17. Also, 3-substituted 1,7-octadiene, 18, is formed as a minor product. So far, the following nucleophiles are known to react with butadiene to form corresponding telomers water, carboxylic acids, primary and secondary alcohols, phenols, ammonia, primary and secondary amines, enamines, active methylene compounds activated by two electron-attracting groups, and nitroalkanes. Some of these nucleophiles are known to react oxidatively with simple olefins in the presence of Pd2+ salts. Carbon monoxide and hydrosilanes also take part in the telomerization. The telomerization reactions are surveyed based on the classification by the nucleophiles. 

Let us follow the role of steric hindrance in a forming product during the course of process according to Komblum and Erickson (1981) as well as Akbulut et al. (1982). Scheme 6.5 clearly demonstrates the effect here, all of the constituent reactions were performed in equal conditions (HMPA as a solvent, at 25°C). The nature was proven for all the cases. The intermediary cumyl radical reacts with the nitroalkane anion, but this reaction is retarded with an increase in the size of an alkyl anion. The significance of the cumyl radical dimerization grows accordingly. 

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. ... 

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. 

Studies into oxidative dimerization have shown that only the persulfate anion is of synthetic value in these reactions. Reaction pH is also crucial with reactions proceeding fastest when a pH of 7.2-9.4 is maintained. " The reaction medium becomes more acidic as the oxidation progresses and needs either buffering or the slow addition of alkali throughout the reaction. If the reaction medium is allowed to become acidic then the starting nitroalkane is regenerated and the Nef reaction predominates. 

Oxidative dimerization gives reasonable yields of vtc-dinitroalkanes for some substrates 2,3-dimethyl-2,3-dinitrobutane (48, 53 %) and 3,4-dimethyl-3,4-dinitrohexane (37 %) are obtained from 2-nitropropane (76) and 2-nitrobutane respectively.However, oxidative dimerization fails to convert 1,1-dinitroethane and trinitromethane into 2,2,3,3-tetranitrobutane and hexanitroethane respectively. Additionally, oxidative dimerisation is not a feasible route for the synthesis of v/c-dinitroalkanes from primary nitroalkanes. Although oxidative dimerization is limited in scope, and yields are often poor, the starting materials are usually inexpensive. 

Nitro-compounds fRNOj) are isomeric with nitrites, but their electronic structure, excited states and photochemistry are very different. There is no very low-lying (n.jt ) state, and nitroalkanes show n — 3i absorption with a maximum around 275 nm ( —201 mol - cm In cyclohexane solution, nitromethane (CH1NOi) is photoreduced to nitrosomethane(CH,NO, but nitroethane under the same conditions gives rise to a nitroso-dimer derived from the solvent CS.47). The latter process is probably initiated by cleavage of the carbon-nitrogen bond in the nitroalkane. In basic solution (when the nitroalkane is converted to a nitronate anion) irradiation can lead to efficient formation of a hydroxamic acid (S.48), and this reaction most likely proceeds through formation of an intermediate three-mem bered cyclic species. 

Benzylic electrophiles bearing electron-withdrawing groups at the arene do not always yield the expected products of nucleophilic substitution on treatment with a nucleophile. One important side reaction is the dimerization of these compounds to yield 1,2-diarylethenes (stilbenes). This dimerization does not require such highly activated systems as the example sketched in Scheme 4.28, but can even occur with, for example, 2- or 4-nitrobenzyl chloride [120, 121]. The latter compounds are converted into the corresponding stilbenes by treatment with KOH in ethanol [120]. Di-arylmethyl halides behave similarly and can yield tetraarylethenes on treatment with a base. These reactions presumably proceed via the mechanism sketched in Scheme 4.27, in which the amphiphilic character of the nitro group plays a decisive role (metalated nitroalkanes or 4-nitrobenzyl derivatives can act as nucleophiles and as electrophiles). 

Halomalonic acid derivatives, 1-halo-l-nitroalkanes [186], and related electrophiles can, upon treatment with a base, also dimerize to yield substituted ethylenes, in the same way as nitrobenzyl halides (see above). The reaction conditions required for this dimerization do not differ much from those required for successful nucleophilic substitution (Scheme 4.46), and if substitution is desired a low concentration of the electrophile should be maintained during the reaction to minimize dimerization. 

On the other hand, Russell and coworkers have proposed that the substitution and enolate dimerization products, formed in the reactions of 2-substituted-2-nitropropanes (XCMe2N02, X = Cl, N02, / -MePhS02) with nucleophiles that easily lose one electron, such as the mono enolate anions ArC(OLi)=CHR (R = Me, Et, z -Pr, zz-Bu) and t-BuC(OLi)=CH2, can be rationalized on the basis of a free radical chain mechanism involving bimolecular substitution or ET reactions between the enolate anion and the intermediate nitroalkane radical anion62. An S 2 -type mechanism has also been recently suggested for the reaction of pentafluoronitrobenzene with several nucleophiles in aqueous media65. 

Dehydration of primary nitroalkanes with phenyl isocyanate or acetic anhydride in the presence of catalytic triethylamine affords nitrile oxides, which may be trapped as their 1,3-dipolar cycloadducts or allowed to dimerize to the corresponding furoxans. Other dehydrating agents that have been used include diketene, sulfuric acid and, when the a-methylene group is activated by electron-withdrawing groups, boron trifluoride in acetic anhydride, trifluoroacetic anhydride with triethylamine, and nitric acid in acetic acid. 

The reaction of nitroalkanes and dinitroalkanes with sodium hydrogen telluride gives nitrosoalkane dimers and olefins, respectively.96 The reduction of other nitrogenated species such as hydroxylamines, azides, nitroso, azo, and azoxy compounds can also be performed by using tellurium reagents.6,11,12... 

MCPBA has been regarded as the reagent of choice for the conversion of primary aliphatic amines into the corresponding nitro compounds. The peroxy acid must be used in excess to minimize formation of dimers of the intermediate nitroso compounds, llie yield of nitroalkane is also increased if the reaction is carried out at elevated temperature, since this favors the monomeric rather than the dimeric foim of the intermediate nitrosoalkane and allows it to be oxidized further. For example, cyclohexylamine gave the dimer of nitrosocyclohexane (43%) when oxidized by MCPBA at 23 C, but at 83 C (in boiling 1,2-di-chloroethane) the only product was nitrocyclohexane (86%). 

Both the above mechanisms are proposed in the literature with Mannich bases of nitroalkanes the substitution is clearly favored by the steric hindrance of the amine moiety, thus suggesting path 1, - whereas NMR studies on the reaction of P-amino-ketones with hydroxy coumarins do not reveal the presence of vinyl ketone intermediates. lodomethylated phenolic Mannich bases arc also claimed to react according to path 2, although the formation as by-products of dimers and methylene-bis-derivatives accounts for the participation of methylenequinone intermediates in the process. "... 

Apart from a few stable species, nitrile oxides exhibit a high tendency toward dimerization to furoxans for this reason, several methods have been developed for the in situ generation of such dipoles in the presence of the desired acceptor. The most common procedures involve thermal or base-mediated deydrohalogenation of hydroxymoyl halides, oxidation of aldoximes, and dehydration of primary nitroalkanes <1984CHEC(6)1>. 

Anodic oxidation of the nitroalkane anion to a radical may lead to dimerization [22], addition to unsaturated systems [23], or substitution in aromatic compounds [24] these reaactions are treated in Chapter 22. 

In aprotic medium reduction of of-halogenated nitroalkanes may yield dimers 2-chloro-2-nitropropane thus yields 2,3-dimethyl-2,3-dinitrobutane [50] in good yield. The reaction has been suggested to be a two-electron reduction to the anion, which in a nucleophilic reaction attacks the substrate. 

An interesting proof has recently been given of photochemical splitting of free radical NO2 from nitroalkane Marciniak and Paszyc [62] irradiated nitro-methane dissolved in cyclohexane and received nitrosocyclohexane dimer ... 

The anions of nitroalkanes (nitronates) can be used as precursors in a connective and regiospecific synthesis of tetrasubstituted alkenes. They are easily formed on reaction with LiOMe and undergo oxidative dimerization in the presence of bromine. The resultant 1,2-dinitroalkanes (Scheme 37) participate in a reductive elimination involving an rc1 radical chain mechanism when irradiated in the presence of Na2S, PhSNa or the lithium nitronate derived from 2-nitropropane. 

In certain cases, 1,3-dipoles containing fluorocarbon groups will participate in cycloadditions to unsaturated hydrocarbons (Scheme 18143 and Eqs. 38144 and 39145 147). The reaction of the nitroalkane derivative 57 probably involves the nitrile oxide 58 as intermediate, since the furoxan product (59) corresponds to a dimer.144 Furoxans have also been obtained... 

Shortly after the Sinay report, additional reports of C-disaccharide syntheses became visible. In 1984, the reported technologies included the dimerization of nitroalkanes as well as the use of hetero Diels-Alder reactions. Beginning with nitroalkane dimerizations, Vasella, et al.,2 initially studied the cross coupling of nitroalkanes and furanoside nitroglycosides discussed in section 2.6 and reviewed in Scheme 8.2.1. As demonstrated in the same report, the dimerization of furanoside nitroglycosides effectively produced C-difuranosides. The specific reaction, shown in Scheme 8.2.2, proceeded under basic conditions and the nitro group was removed on treatment with sodium sulfide. 

Telomerization is defined as an oligomerization of dienes accompanied by addition of a heteroatom or carbon nucleophilic reagent10. It is catalyzed by various organometallic compounds of transition metals, especially palladium compounds. The nucleophiles, such as water, alcohols, amines or carboxylic acids, as well as enamines, nitroalkanes and stabilized carban-ions, are mainly introduced in the terminal position of the dimeric molecule in excellent yield10. It is also possible to direct the reaction towards an internal product functionalization. Telo-merizations with heteronucleophiles are regarded as heterocarborative addition reactions and are described in Section 1.5.8.4. 

While relatively few examples have been reported, nitroalkanes can serve as efficient carbon nucleophiles in the Pd-catalyzed linear dimerization reaction.t For example, butadiene reacts with 2-nitropropane (137, (Ph3P)2PdCl2, KOH, i-PrOH, 50 °C, 4 h) to afford 9-methyl-9-nitro-l,6-decadiene (138 R , = Me) in 89% yield (Scheme 44). Nitromethane... 

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