Synthesis of nitro compounds

Indirect conversion of oximes to nitro compounds viact-halo nitro compounds has provided a useful method for synthesis of nitro compounds, as shown m Scheme 2 1... 

In general, azides are more easily available than rutro compounds by S 2 reacnon of the corresponding halides Thus, the direct conversion of an azide mto a nitro group is useful for the synthesis of nitro compounds Corey and coworkers have reported the easy cc azides to nitro compounds via ozonolysis of phosphine irrunes fEq 2 70 ... 

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... 

Table 2.4 Synthesis of nitro compounds from halides...

SYNTHESIS OF NITRO COMPOUNDS BY OXIDATION 2.2.1 Oxidation of Amines... 

Until recently there were few cases in which an alkali nitrite could replace silver nitrite in the synthesis of nitro compounds. Such a case was Kolbe s nitroalkane synthesis, in which an alkali salt of a 2-haloalkanoic acid was treated with a boiling aqueous solution of an alkali nitrite the 2-nitroalkanoic acid formed lost carbon dioxide under the reaction conditions and the nitroalkane distilled over in the steam. The Kolbe synthesis is, however, of practical use only for the preparation of nitromethane (38% yield from chloro-acetic acid648) and nitroethane (about 50% yield from 2-bromopropionic acid649) it is substantially valueless for higher fatty acids.649,650... 

Chemoselective C-alkylation of the highly acidic and enolic triacetic acid lactone 104 (pAl, = 4.94) and tetronic acid (pA, = 3.76) is possible by use of DBU[68]. No 0-alkylation takes place. The same compound 105 is obtained by the regioslective allylation of copper-protected methyl 3,5-dioxohexano-ate[69]. It is known that base-catalyzed alkylation of nitro compounds affords 0-alkylation products, and the smooth Pd-catalyzed C-allylation of nitroalkanes[38.39], nitroacetate[70], and phenylstilfonylnitromethane[71] is possible. Chemoselective C-allylation of nitroethane (106) or the nitroacetate 107 has been applied to the synthesis of the skeleton of the ergoline alkaloid 108[70]. 

A new multicomponent reaction of nitro compounds with isocyanides gives ct-oxyimi-noamides, which are important for dnig synthesis such as cephiilosporin and fi-lactamase inhibitor fEq 6 65 Multicomponent reactions using isocyanides fUgi reacdoni is re-... 

Denitration of nitro compounds with Bu- SnD provides an elegant method fci the synthesis of deiuerated compounds Recently, the synthesis of deuterium labeled plant sterols has been reported fsee Eq 11%)... 

For a review of nitro compounds in organic synthesis, see Tamura, R. Kamimura, A. Ono, N. Synthesis... 

The synthesis of aromatic amines is an active and important area of research.2 Many methods are available in the literature for the synthesis of these compounds. Though some of these are widely used, still they have limitations based on safety or handling considerations. For example, catalytic hydrogenation3 of nitro or azido compounds in the presence of metals such as palladium on carbon or Raney nickel require stringent precautions because of their flammable nature in the presence of air. In addition, these methods require compressed hydrogen gas and a vacuum pump to create high pressure within the reaction flask. To overcome these difficulties, several new methods have been reported in the... 

The condensation of nitro compounds and imines, the so-called aza-Henry or nitro-Mannich reaction, has recently emerged as a powerful tool for the enantioselective synthesis of 1,2-diamines through the intermediate /3-amino nitro compounds. The method is based on the addition of a nitronate ion (a-nitro carbanion), generated from nitroalkanes, to an imine. The addition of a nitronate ion to an imine is thermodynamically disfavored, so that the presence of a protic species or a Lewis acid is required, to activate the imine and/or to quench the adduct. The acidic medium is compatible with the existence of the nitronate anion, as acetic acid and nitromethane have comparable acidities. Moreover, the products are often unstable, either for the reversibility of the addition or for the possible /3-elimination of the nitro group, and the crude products are generally reduced, avoiding purification to give the desired 1,2-diamines. Hence, the nitronate ion is an equivalent of an a-amino carbanion. 

A famous example of the use of nitro compounds in synthesis was the original synthesis of the antibiotic chloramphenicol (8), which is still used to treat tropical diseases. This synthesis also confirmed the structure of chloramphenicol and established that the (-)-thrco compound was the biologically active stereoisomer. 

The synthesis of nitro dyes is relatively simple, a feature which accounts to a certain extent for their low cost. The synthesis, illustrated in Scheme 6.5 for compounds 140 and 141, generally involves a nucleophilic substitution reaction between an aromatic amine and a chloronitroaromatic compound. The synthesis of C. I. Disperse Yellow 14 (140) involves the reaction of aniline with l-chloro-2,4-dinitroaniline while compound 141 is prepared by reacting aniline (2 mol) with compound 144 (1 mol). 

A number of nitro compounds used in natural product synthesis have been prepared by the nitration of alkyl halides. Some recent examples are summarized in Table 2.4. 

Another application of diastereoselective nitro-aldol reactions catalyzed by Bu4NF-3H20 is demonstrated in a simple synthesis of l,4-dideoxy-l,4-imino-D-mannitol (DIM) and amino analogues (Eq. 3.85).134 The nitro-aldol reaction of nitro compounds bearing a-oxy or a-amino function with glyceraldehyde leads to nitrohexitols, which can be reduced to the corresponding amino compounds. Cyclization gives iminopolyols, as shown in Eq. 3.85. 

---