Ladenburg reduction

Piperideines unsubstituted at the nitrogen atom may be prepared from the corresponding pyridine compounds by partial reduction with sodium and boiling alcohols (the Ladenburg reduction), by electrolytic reduction, or, preferably, by reduction with aluminum hydride. l-Alkyl-3-piperideines are prepared by reduction of quaternary pyridinium salts with formic acid (the Lukes reduction) or with complex hydrides. 

In the early investigations on the Ladenburg reduction there were some observations of the formation of tetrahydro derivatives, but the... 

The Ladenburg reduction of 3-methylpyridine,47 4-methyl-pyridine,47 4-ethylpyridine,48 and 2-methyl-5-ethylpyridine48 was... 

The Ladenburg reduction of 4-sec-butylpyridine gives a mixture of a saturated and an unsaturated base, the latter probably being 4-sec-butyl-3-piperideine.50... 

The parent 3-piperideine (3) was first prepared (in the form of its hydrochloride) by Ladenburg reduction of 4-pyridone, conversion of the resulting 4-piperidinol into 4-bromopiperidine, and dehydro-halogenation of the latter.52... 

Two 3-piperideines (63 and 64) and two piperidines (cis and trans isomers) are obtained by the Ladenburg reduction of 4-ethyl-3-methyl-pyridine, whereas only one tetrahydro base, namely, 4,6-dimethyl-3-piperideine (65), results from 2,4-dimethylpyridine, in addition to the piperidines.48... 

Ladenburg reduction of 2,4,6-trimethylpyridine affords a mixture of cis-2,4,6-trimethyl-3-piperideine (66) and all three isomeric 2,4,6-trimethylpiperidines.5 4... 

The aluminum hydride reduction of pyridine bases is very advantageous in the preparation of 3-piperideines since the amount of the corresponding accompanying hexahydro bases is small. The resulting tetrahydropyridines possess the same constitution as those obtained by the electrolytic or Ladenburg reduction (see Table III). 

Reduction of quaternary pyridinium halides (or, more precisely, formates) with formic acid in the presence of potassium formate at about 150°C is usually referred to as the Lukes reduction.80-95 Instead of potassium formate, triethylamine may be used, especially with quaternary pyridinium iodides.85,86 Mixtures of l-alkyl-3-piperideines (77) and 1-alkylpiperidines (78) are usually obtained. Formation of piperideines (77) might be explained by analogy with the Ladenburg reduction of pyridine bases the double bond at position 3 is resistant toward further reduction by formic acid or by... 

Concerning the other possibility, the isomerization of 3-piperideines (111) to 4-piperideines (113), the mixtures of 3-methyl-4-ethyl-3-piperideine (116) and 4-ethyl-5-methyl-3-piperideine (117), and of l,3,4-trimethyl-3-piperideine (118) and l,4,5-trimethyl-3-piperideine (119) were found to be quite stable to the prolonged action of dilute sulfuric acid (conditions of electrolytic reduction), dilute alkali (conditions of isolation procedures), sodium alkoxides (conditions of the Ladenburg reduction), and aluminum hydride.61... 

Methods A, AIH3 reduction B, electrolytic reduction C, Ladenburg reduction B, NaRH reduction E, L4AIH4 reduction ... 

Starting with three pounds each of the zinc diethyl and ethyl silicate, Ladenburg prepared all of the ethylethoxysilanes and described their properties. He also was able to show that the reaction was not a simple reduction of ethoxy groups to ethyl groups by the action of sodium, for methyl silicate and zinc ethyl gave e %imethoxysilanes. It is probable that the sodium reacted first with the zinc alkyl, as proposed by Ladenburg,... 

Conine is also of especial interest because it is the first natural alkaloid to have been made synthetically. In 1886 Ladenburg prepared it from a//>/fa-picoline which is alpha-m hy pyridine. By condensing this with acetaldehyde he obtained alpha-dXLy pyridine and by reduction this yielded the corresponding saturated compound, viz., alpha-yroyyl piperidine. This proved to be inactive conine and from it the dextro and levo isomers were obtained. The dextro conine thus prepared is identical with the natural alkaloid of hemlock. The reactions are as follows ... 

Finally, pyridine derivatives can be reduced by metals. Piperidine is obtained from pyridine with sodium in alcohols Ladenburg reaction) piperidines, as well as tetrahydropyridines, are obtained from 4-alkylpyridines. A -Alkylpyridinium ions are converted into 7V-alkylpiperidines by metals such as Zn or Sn in an acidic medium, or by electrochemical reduction (122 - 125, see p 293). 

Reduction of pyridine derivatives can be accomphshed by metals. Sodium in alcohol solvents reduces pyridine to piperidine (Ladenburg reaction), and N-alkylpyridinium ions are converted to N-alkylpiperidines by metals (such as Sn or Zn) in acidic medium or by electrochemical reduction. 

Ladenburg 38 described the reduction of pyridine and some of its homologues to piperidines by sodium and alcohol, and the method has occasionally been used for this purpose it is useful with pyridine-carboxylic acids and their side-chain vinylogues which give piperidine-carboxylic acidsi 40 Esters of pyridine-carboxylic and vinylogous side-chain acids give the fully saturated alcohols. ... 

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