Reduction of Schiff’s base

The reduction of Schiff s bases is a well used and convenient method for the preparation of secondary amines. Selenophenol has now been found to be an excellent and advantageous reagent to effect this, and the reductive alkylation of amines with carbonyl compounds. The preparation of tertiary amines bearing three different substituents can also be achieved by the successive addition of carbonyl compounds to a primary amine in a one-pot reaction (Scheme 15). The... 

However, it is not always possible to obtain one-electron waves even in aprotic solvents in [53], for example, it was shown that during the electrolytic reduction of Schiff s bases - benzalaniline derivatives - a two-electron wave is formed in nearly all cases, although as a result of large-scale electrolysis at the half-wave potential it was possible to detect the formation of dimeric products (from the nature of the infrared spectra and of cryoscopic measurements). Such polarographic behavior is explained by the instability of the intermediate radical anions. 

Aromatic nitro compounds are often strongly colored. They frequently produce characteristic, colored, quinoid derivatives on reaction with alkali or compounds with reactive methylene groups. Reduction to primary aryl amines followed by diazotization and coupling with phenols yields azo dyestuffs. Aryl amines can also react with aldehydes with formation of Schiff s bases to yield azomethines. 

While enamines can usually be obtained directly from ketones and secondary amines their formation by an indirect route may bo advantageous. The previously mentioned condensation of rnethyl ketones during azeotropic enamine formation has prompted the alklyation (J) or acylation and reduction (59) of Schiff s bases. A parallel method uses the formation and desulfurization of N-acylthiazolines followed by hydride reduetion (60,61). 

Consequently, Dehmlow and coworkers modified the cinchona alkaloid structure to elucidate the role of each ofthe structural motifs of cinchona alkaloid-derived chiral phase-transfer catalysts in asymmetric reactions. Thus, the quinoline nucleus of cinchona alkaloid was replaced with various simple or sterically bulky substituents, and the resulting catalysts were screened in asymmetric reactions (Scheme 7.2). The initial results using catalysts 8-11 in the asymmetric borohydride reduction of pivalophenone, the hydroxylation of 2-ethyl-l-tetralone and the alkylation of SchifF s base each exhibited lower enantiomeric excesses than the corresponding cinchona alkaloid-derived chiral phase-transfer catalysts [14]. 

An asymmetric synthesis of 2-amino-4-phosphonobutanoic acid has been developed from diethyl 3-oxo-4-(ethoxycarbonyl)propylphosphonate and L-( -nf/fro-(lS,27 )-l,2-diphenyl-2-hydrox-ylamine as chiral source. Formation of Schiff s base and acid-catalyzed transesterification are successfully performed in boiling n-BuOH. After reduction of the imino linkage with Al-Hg in moist DME, debenzylation [H2, PdiUll) 7( and hydrolysis with 4 M HCl, (7 )-(-)-2-amino-4-phosphonobutanoic acid is isolated in 66% yield and 67% ee. ... 

The persubstituted N-methanesulfonates N-methanesulfinates and Schiff s bases of kanamycin A show the same MIC values as the parent compound due to their ability to hydrolyse under physiological conditions. The NaBH4 reduction of suitably substituted Schiff s bases affords tetra-N-phenylalkyl derivatives of kanamycin A ° which show activity only in some cases. The first attempted modifications have been the reactions at the 6 -hydroxyl group of kanamycin A. Through protection of the amino groups by preparations of Schiff s bases, acetates or carbamates, the 6"-hydroxyl group is modified to lead to the derivatives, shown in Table 7. 

Synthesis and Reaction.—No less than three different groups " have described various extensions to the general method for the homolagation of a-amino-acids by the reactions of electrophiles with enolates derived from Schiff s bases of a-amino-esters, originally reported by Stork s group last year. A full report has appeared on the electro-reductive coupling of Schiff s bases of a-amino-esters with alkyl halides yields of a-alkylated amino-acids are between 36 and 86%... 

Pyridoxal Derivatives. Various aldehydes of pyridoxal (Table 3) react with hemoglobin at sites that can be somewhat controlled by the state of oxygenation (36,59). It is thereby possible to achieve derivatives having a wide range of functional properties. The reaction, shown for PLP in Figure 3, involves first the formation of a Schiff s base between the amino groups of hemoglobin and the aldehyde(s) of the pyridoxal compound, followed by reduction of the Schiff s base with sodium borohydride, to yield a covalendy-linked pyridoxyl derivative in the form of a secondary amine. 

Macrocycles have been prepared by formation of macrocyclic imines as well as by using variations of the Williamson ether synthesis ". Typically, a diamine or dialdehyde is treated with its counterpart to yield the Schiff s base. The saturated macrocycle may then be obtained by simple reduction, using sodium borohydride, for example. The cyclization may be metal-ion templated. In the special case of the all-nitrogen macrd-cycle, 15, the condensation of diamine with glyoxal shown in Eq. (4.14), was unsuccess-ful ... 

This was confirmed by an independent analytical method by Spath and Boschan, and by a synthesis of pellotine by Spath and Becke, starting from the benzyl ether of 2-hydroxy-3 4-dimethoxyacetophenone, which was converted by aminoacetal into the Schiff s base (V). This, on treatment with sulphuric acid (73 per cent.), followed by warm water, gave 8-hydroxy-6 7-dimethoxy-l-methyh 5oquinoline (VI), of which the methiodide, m.p. 188-189-5°, on reduction furnishes pellotine (IV). From dZ-pellotine so formed Spath and Kesztler, by a special process of fractionation, isolated 1-pellotine having — 15-2° (CHCI3), for which... 

The last reaction perhaps involves an intermediate such as 33a which expells a proton and dimethyl sulfide. Formation of the Schiff s base with t-butylamine, reduction with sodium borohydride and hydrogenolysis of the benzyl ether produces sulfonterol (28). Despite the fact that the methylene hydrogen of sulfonterol must be much less acidic than of the corresponding urea proton on carbuterol or the sulfonamide proton on soterenol, good bioactivity is retained. 

Two aldehydic nucleotide derivatives have found use as affinity labels. The magnesium salt of (64), formed by oxidation of ATP with periodate, is a competitive inhibitor of pyruvate carboxylase with respect to [Mg. ATP2-],100 and (65), obtained from the / -anomer of 5-formyluridine-5 -triphosphate on treatment with alkali, is a non-competitive and reversible inhibitor of DNA-dependent RNA polymerase from E. coli.101 In each case, addition of borohydride gives stoicheiometric covalent linkage of the nucleotide to the enzyme, with irreversible inactivation. It is thought that condensation with lysine occurs to give a Schiff s base intermediate, which undergoes subsequent reduction. 

To circumvent this problem, several methods have been developed (157). Probably, the most prominent method is treatment with sodium boro-hydride (0.1% in PBS, 30 minutes prior to staining). NaBILi is known to neutralize Schiff s bases through reduction of amine-aldehyde compounds into nonfluorescent salts. 

Moghaddam, F.M., Khakshoor, O. and Ghaffarzadeh, M., Microwave assisted reduction of Schiff bases by triethylammonium formate/formic acid system, /. Chem. Res. (S), 2001, 525-527. 

Electrochemical reduction of imines (25 Schiff bases) in acidic media proceeds via the iminium species, i.e. the protonated imine (26) (Scheme 5)29. Since 26 bears a positive charge, it is very easily reduced, so much so that the resulting neutral radical (27) is formed at a potential positive of its reduction potential. The products are therefore derived from 27 rather than the corresponding carbanion (28). This stands in contrast with the electrochemical behavior of imines in neutral media, where 27 is immediately reduced to 2830. Thus, cathodic reduction of /u. s-irnincs of 1,2-diamines (29) in DMF containing methanesulfonic acid affords tetrahydropyrazines (equation 13)31. A similar reaction can... 

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