Reduction of Schiff bases

The 6/3-amino group of 6-APA may be alkylated either with diazoalkanes <67LA(702)163) or by the reduction of Schiff bases (Scheme 50) (65JCS3616). Two special cases of N-alkylation are also shown in Scheme 50 the formation of an imidazolidinone ring upon treating ampicillin with acetone (66JOC897), and the formation of a 6/3-amidinopenicillanic acid from 6-APA (77MI51105). 

The conjugate may be stabilized by addition of a reductant such as sodium borohy-dride or sodium cyanoborohydride. Usually sodium cyanoborohydride is recommended for specific reduction of Schiff bases, but since the conjugate has already formed at this point, the use of sodium borohydride will both reduce the associated Schiff bases and eliminate any remaining aldehyde groups. Add sodium borohydride to a final concentration of lOmg/ml. Continue to react for 1 hour at 4°C. 

Reduction of Schiff base (XXXI) formed between l-phenethyl-4-piperidone and aniline, and acylation of the resultant dibase gives the highly potent analgesic [112] fentanyl(Sublimaze,XXXIla). In mice (tail-clip method), fentanyl... 

Incubate at RT on a shaker for 2 h, then add 1/10 vol. of Soln. E and mix again. Allow the reduction of Schiff bases at 4 °C for 2 h, and then dialyze against PBS overnight. Instead of dialysis, a gel filtration on a Sepahdex G-25 column, equilibrated with PBS, is possible. Concentrate the brownish dialysate and eluate, respectively, and add BSA to a final concentration or 10 mg/ml, mix with an equal volume of glycerol, and store at 20 °C. 

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. 

Unsymmetrical secondary amines are readily prepared in good yields by the catalytic reduction of Schiff bases at moderate temperatures in high-or low-pressure equipment. Many examples have been cited. The intermediate imines are prepared from primary amines and aldehydes—very seldom from ketones—and may be used without isolation (cf. method 431). For the preparation of aliphatic amines, e.g., ethyl-w-propylamine and n-butylisoamylamine, a prereduced platinum oxide catalyst is preferred with alcohol as the solvent. Schiff bases from the condensation of aromatic aldehydes with either aromatic or aliphatic amines are more readily prepared and are reduced over a nickel catalyst. In this manner, a large number of N-alkylbenzylamines having halo, hydroxyl, or methoxyl groups on the nucleus have been made. Reductions by means of sodium and alcohol and lithium aluminum hydride have also been described,... 

The starting materials are readily available by dialkylation of benzyl-amine or by the monoalkylation of alkylbenzylamines, which in turn are prepared by the reduction of Schiff bases (method 429). The method has been extended to the formation of hydroxy amines, amino esters, and amino acids. ... 

The borohydride reduction of Schiff base formed between a protein and pyridoxal phosphate should be carried out at a mildly acidic pH. Although sodium borohydride is more unstable in acidic solution, this disadvantage is offset by the exceptional reactivity of the Schiff base salts which are formed in mildly acidic solution (pH 4.S-6.5) (Schellen-berg 1963). Reductions have been carried out after the protein and pyridoxal-5-phosphate have been incubated at a pH of 7.5 which is then changed to 4.5 or 6.5 with acetic acid (Rippa et al. 1967 Dempsey and Christensen 1962 Piszkiewicz et al. 1970) or after initial incubation at pH 6.0 (Schnackerz and Noltmann 1971). The relative merit of either... 

Lukasiewiez, A. Mechanism of chemical reactions. I. Mechanism of the Leuckart-Wallach reaction and of the reduction of Schiff bases by... 

Reduction of ketones. In usual solvents trimethylamine borane reacts with ketones only very slowly even at steam bath temperature, but in the presence of boron trifluoride etherate it is an effective reducing agent 4-r-butylcyclohexanone is reduced rapidly to a mixture of 46% of the cis alcohol and 54% of the trans isomer. Reduction of Schiff bases. Schiff bases, for example benzylideneaniline from ben-zaldehyde and aniline, are reduced rapidly and efficiently by the reagent in solution or suspension in acetic acid. Unlike other borohydrides, trimethylamine borane... 

REDUCTION OF SCHIFF BASES USING RUTHENIUM COMPLEXES BY MOLECULAR HYDROGEN. 

The complexes of ruthenium of the formula RUCI3L2 Where L is benzimidazole (BzlH), 2-Methylbenzimidazole (2-MebzlH), 2-Ethylbenzimidazole (2-EtbzlH) and 2-propyl benzimidazole (2-PrbzlH) acts as homogeneous catalysts in dimethylformamide in the presence of sodiumborohydride for the reduction of Schiff bases to secondary amines. The reactions were carried out at 30 C and 1 atmosphere of hydrogen pressure. Kinetic studies reveal that the reaction has depencence on [Catalyst] and [Schiff base] in the concentration ranges studied. 

The ruthenium complexes studied serve as efficient catalyst precursors in the reduction of Schiff bases of atmospheric pressure of hydrogen and at room temperature. The reduction of one functional group in presence of pther reducible groups have been observed. For example, in the case of Schiff bases containing NO2 groups only >C=N moiety is reduced. Thus selectivity has been observed. Preliminary kinetic experiment reveal that the hydrogen uptake has a first order dependence on [catalyst] and [substrate] in the concentration ranges studied. 

Stereochemical aspects of the reduction of Schiff base at C-4 with NaBH ... 

Fluorinated synthons have been used to access fluorinated imidazoles. Reduction of Schiff bases derived from amidines and hexafluoroacetone with SnCl2 gives rise to 5-fluoro-4-trifluoromethylimidazoles 110 (Fig. 3.57). ° ° Because the 5-fluoro substituent is readily displaced by nucleophiles such as alkoxide, cyanide, and others, this procedure provides access to a range of trifluoromefliyl-substituted imidazoles (also see below). 

Reduction of Schiff-bases has been performed also with hydrogen transfer reactions catalyzed by RhCl(PPh3)3, RhCl(CO)(PPh3)2, and... 

Catalytic reduction of Schiff bases has also been used to produce side-chain aminopyridines. 2-Acetylpyridine condenses with ethylene diamine to give an imine which is reduced with hydrogen in the presence of platinum oxide to give iV,iV-bis[a-(2-pyridyl)ethyl]ethylenediamine (IX-239). Table IX-65 lists... 

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