Nitro retention

The iacreased chemical stabiUty of the 6-deoxytetracyclines allows chemical modification with retention of biological activity electrophilic substitutions have been carried out at C-7 and C-9 under strongly acidic conditions (46—53). Reactions of 6-deoxy-6-demethyltetracycline [808-26-4] (16), C21H22N2O7, with electrophiles, such as nitrate ion (49), bromomium ion (46,47) (from N-bromosuccinimide), or N-hydroxymethylphthalimide (53), yielded 7-substituted tetracyclines. In the case of the nitration reaction, both the 7- and 9-nitro isomers (17, X = NO2, Y = H) and (17, X = H, Y = NO2) were obtained. 

Dimtrogen tetroxide is the most versatile of the nitrosating reagents and, in addition, it is readily available. The nitro-soamide method of deamination gives far superior yields and much less skeletal isomerization than the nitrous acid method (which is essentially limited to aqueous media), and it leads to a greater retention of optical activity than the triazene method3... 

P-Nitro alcohols can be hydrogenated to the corresponding amino alcohols with retention of configuration the stereoselective Henry reaction is a useful tool in the elaboration of pharmacologically important P-amino alcohol derivatives including chloramphenicol, ephedrine, norephedrine, and others. Some important P-amino alcohols are listed in Scheme 3.11.107... 

They react with a wide range of aliphatic and aromatic aldehydes in the presence of catalytic amounts of tetrabutylammonium fluoride (TBAF) to give the trialkylsilyl ethers of P-nitro alcohols with high anti-selectivity (98%). The diastereoselective Henry reaction is summarized in Table 3.2. The products are reduced to P-amino alcohols using Raney Ni-H2 with retention of the configuration of P-nitro alcohols (Scheme 3.12). 

Ono and Kamimura have found a very simple method for the stereo-control of the Michael addition of thiols, selenols, or alcohols. The Michael addition of thiolate anions to nitroalkenes followed by protonation at -78 °C gives anti-(J-nitro sulfides (Eq. 4.8).11 This procedure can be extended to the preparation of a/jti-(3-nitro selenides (Eq. 4.9)12 and a/jti-(3-nitro ethers (Eq. 4.10).13 The addition products of benzyl alcohol are converted into P-amino alcohols with the retention of the configuration, which is a useful method for anri-P-amino alcohols. This is an alternative method of stereoselective nitro-aldol reactions (Section 3.3). The anti selectivity of these reactions is explained on the basis of stereoselective protonation to nitronate anion intermediates. The high stereoselectivity requires heteroatom substituents on the P-position of the nitro group. The computational calculation exhibits that the heteroatom covers one site of the plane of the nitronate anion.14... 

Amino alcohols like (iS )-prolinol react with nitroalkenes very rapidly with very high facia] selectivity.31 Rapid and stereoselective reduction of the nitro function is essential for the conversion of the products to 1,2-diamine derivatives with the retention of the configuration. Samarium diiodide is recommended in the stereoselective reduction of thermally unstable 2-aminonitroalkanes to give a range of useful 1,2-diamines (Eq. 4.26).32... 

The reduction of P-nitro alcohols with ammonium formate in the presence of Pd/C also proceeds with retention of their configurations (Eq. 6.52).98... 

The specific solvation of NO coordinated to Fe(III) and the resulting solvent reorganization upon NO dissociation (Fig. 3) finds some analogy with the nitrophorins, which are heme protein systems for NO transfer found in certain blood sucking insects. The crystal structure of one nitro-phorin, NP4, shows that binding of NO to the Fe(III) center leads to a collapse of the protein around the coordinated NO. The distal hemebinding pocket in nitrophorin NP4 is quite open to solvent in the absence of NO. It was postulated that collapse of the protein around the heme nitrosyl led to increased retention of bound NO at low pH (25). 

Substitution of fi-nitro sulfides.2 (3-Nitro sulfides in the presence of a Lewis acid undergo displacement reactions with either allyl- or cyanotrimethylsilane. The reaction is considered to involve an episulfonium intermediate, which is then substituted at the more positive carbon (equation I). The reaction proceeds with retention of configuration, and anti (J-nitro sulfides react much more rapidly than... 

The mechanism of the novel transformation of a-nitro- to a-hydroxy-ketones has been probed. The reaction, which proceeds under basic aqueous conditions, requires that the Q -nitro substrate be CH-acidic in the a -position, and that it be readily depro-tonated under the conditions employed. NO2 -OH exchange occurs with retention of configuration, with the hydroxyl oxygen being predominantly derived from the solvent. A mechanism involving neighbouring-group participation, via a Favorskii-like cyclopropanone intermediate, is proposed. 

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). 

The reaction has been carried out on large- and small-scale batches (Note 10). This modification,8 as exemplified by 3,4,5-trimethoxybenzaldehyde, has been applied by the submitters to the preparation of other aldehydes9 such as 3,4-dimethyl-benzaldehyde10 (90% yield), 3-benzyloxy-4,5-dimethoxybenz-aldehyde11 (88% yield, with retention of the benzyl group), and 3-methoxy-4-nitrobenzaldehyde12 (62% yield, with retention of the nitro group). 

Phases with phenyl groups are less retentive than C8 bonded phases. They show a pronounced selectivity and retention toward solutes with aromatic ring systems, attributed to n-n interactions. These n-n interactions can be improved when nitro substituted phenyl groups are bonded to silica. The strongest interactions have been reported with tetra nitro or tetra chloro phthalimide substituents. 

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