Nitro compounds with Grignard reagents

Today, many stable radicals are known, as shown in Figures 1.11 and 1.12. However, most of them are nitroxyl radicals like NO or N02. Standard generation methods of nitroxyl radicals are as follows. One is the oxidation of amines or hydroxyamines by Pb02, or by less toxic oxidants such as oxone, Cu(OAc)2, mCPBA (eqs. 1.13 and 1.14). Another one is the reaction of nitro compounds with Grignard reagents (eq. 1.15) [9-14]. 

Recently Bartoli and co-workers [85-87] have published a number of papers dedicated to the systematic study of the reaction of aromatic nitro compounds with Grignard reagent. They confirmed the nucleophilic character of the alkylation of the ring. They also found that under their experimental conditions the nitro group was reduced to the nitroso group (17) ... 

The conjugate bases of nitro compounds (formed by treatment of the nitro compound with BuLi) react with Grignard reagents in the presence of C1CH= NMe Cr to give oximes RCH =N(0)0Li + R MgX RR C=NOH. ... 

Addition of organometallic reagents to nitro compounds is possible but is sparingly used. Reaction of aromatic nitro compounds with large excess of phenyl magnesium bromide produces hydroxylamines in moderate yield . Similar addition of Grignard compounds to nitromethane proceeds in low yield ° while addition of excess methyllithium to tertiary nitro compound 113 results in formation of hydroxylamine 114 (equation 83) . ... 

Action of bases in nucleophilic reactions of nitro compounds Action of Grignard reagent on nitro aimpounds Reaction of aromatic nitro compounds with diazomethane... 

Primary Amines—Several new and improved methods for the preparation of aromatic primary amines have been described. " The catalytic reduction of aromatic nitro-compounds to amines with hydrazine hydrate in the presence of iron(iii) oxide hydroxide proceeds smoothly and in high yields. Nitroarenes (1) react with Grignard reagents in the presence of copper(i) iodide, and are alkylated selectively on the aromatic moiety, accompanied by reduction of the nitro-group to the amine (Scheme 1). Both aryl and alkyl azides are rapidly... 

The latter reagent also methylates certain heterocyclic compounds (e.g., quinoline) and certain fused aromatic compounds (e.g., anthracene, phenanthrene). The reactions with the sulfur carbanions are especially useful, since none of these substrates can be methylated by the Friedel-Crafts procedure (11-12). It has been reported that aromatic nitro compounds can also be alkylated, not only with methyl but with other alkyl and substituted alkyl groups as well, in ortho and para positions, by treatment with an alkyllithium compound (or, with lower yields, a Grignard reagent), followed by an oxidizing agent such as Bra or DDQ (P- 1511). 

Alkyl lithium and alkyl Grignard reagents react with aromatic nitro compounds in a similar way to give alkylated products (Eq. 9.23).37... 

Similar to the formation of allylmagnesium chloride (25), the oxidative addition of allyl halides to transition metal complexes generates allylmetal complexes 26. However, in the latter case, a 7i-bond is formed by the donation of 7i-electrons of the double bond, and resonance of the n-allvl and 7i-allyl bonds in 26 generates the 7i-allyl complex 27 or (/ -allyl complex. The carbon-carbon bond in the 7i-allyl complexes has the same distance as that in benzene. Allyl Grignard reagent 25 is prepared by the reaction of allyl halide with Mg metal. However, the 7i-allyl complexes of transition metals are prepared by the oxidative addition of not only allylic halides, but also esters of allylic alcohols (carboxylates, carbonates, phosphates), allyl aryl ethers and allyl nitro compounds. Typically, the 7i-allylpalladium complex 28 is formed by the oxidative addition of allyl acetate to Pd(0) complex. 

The most conspicuous property of aliphatic amines, apart from their fishy smell, is their high basicity, which usually precludes N-alkylations under acidic reaction conditions (last reaction, Scheme 6.3). Hence, alkylation of amines with tertiary alkyl groups is not usually possible without the use of highly stabilized carbocations which can be formed under basic reaction conditions. Rare exceptions are N-alkyla-tions of amines via radicals (Scheme 4.2), copper-catalyzed propargylations (Scheme 6.3), and the addition of amines to some Michael acceptors and allyl palladium or iridium complexes. Better strategies for the preparation of tert-alkylamines include the addition of Grignard reagents to ketone-derived imines [13] or the reduction of tert-alkyl nitro compounds. 

Reactions of allylic and benzylic Grignard reagents with alkyl nitro compounds can, under the right conditions, provide an acceptable route to nitrones [11]. Lack of regio- and stereoselectivity may be a problem, though the former can be controlled to some extent by varying the acid used for protonation, e.g. 

Uncatalyzed nncleophihc snbstitution reactions of Grignard reagents with aromatic compounds is much more difficult than with alkyl species, unless the leaving gronp (sometimes halide nsnally alkoxide is preferred) is activated by one or more potent electron-withdrawing substituents, snch as an oxazoline, nitro, or ester moiety, most often at the ortho... 

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