Ladenburg reaction

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). 

Although the first benzimidazole was prepared by Hobrecker in 1872, it was Ladenburg who extensively explored the preparation of benzimidazole derivatives by the condensation between ort/to-amino aniline and carbonyl compounds (aldehydes and ketones) in 1875. Subsequently, Phillips further extended Ladenburg s preparation to the condensation between ort/io-amino aniline and acetic acid to produce different kinds of carboxylic acids in the presence of dilute mineral acid. Therefore, the preparation of benzimidazole from ort/io-amino aniline is referred to as the Ladenburg method," Phillips method, Phillips modification, or the Phillips-Ladenburg reaction. It has been proposed that the condensation between ortho-dxaim aniline and carbonyl compounds involves the formation of a Schiff base intermediate," whereas the condensation between ort/io-amino aniline and acid proceeds via the A,lV -diacyl and monoacyl intermediated This condensation generally works for aliphatic acids and is feasible for aromatic acids if the condensations are carried out above 180°C in sealed reaction vessels. ... 

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 reaction, of pyridine 367 Larock synthesis (isoquinoline) 416 Lautens synthesis (indole) 141... 

Quinolinium 2-dicyanomethylene-1,1,3,3-tetracyanopropanediide dimensions, 2, 110 Quinolinium iodide, 1-alkyl-Ladenburg rearrangement, 2, 300 Quinolinium iodide, 1-methyl-Ladenburg rearrangement, 2, 300, 335 Quinolinium iodide, [l-methyl-4-[3(5)-pyrazolyl]-blood sugar level and, 5, 291 Quinolinium perchlorate, 1-ethoxy-hydroxymethylation, 2, 300 Quinolinium perchlorate, 1-methyl-nitration, 2, 318 Quinolinium salts alkylation, 2, 293 Beyer synthesis, 2, 474 electrophilic substitution, 2, 317 free radical alkylation, 2, 45 nitration, 2, 188 reactions... 

Silicon tetrachloride reacts with acetic anhydride to form sihcon tetraacetate (tetraacetoxysilane). This reaction was discovered by Friedel and Ladenburg in 1867 ... 

Alkylpyridinium halides give mixtures of alkylpyridines on heating, e.g. (964) gives 2- and 4-picoline, with other minor products. This reaction is known as the Ladenburg rearrangement, and involves /V-alkyl bond homolysis. 

The exchange of substituents between molecules or parts of molecules has been observed for many years. Probably one of the first such observations dates back to the 19th century when Ladenburg (93, 147) detected the presence of a diphenylsilicon derivative in the reaction product of the alkylation of phenyltrichlorosilane with dialkylzinc. He concluded that this... 

The close relationship between organosilicon chemistry and organometallic chemistry is confirmed by a reaction formulated by Ladenburg in 1874 ... 

Substitution by Alkyls of Zinc, Mercury, and Aluminum. The reaction of alkyls of zinc with ethyl silicate or silicon tetrachloride was the first to be used for the preparation of organosilicon compounds. During the period 1863 to 1880 Friedel and Crafts and later Ladenburg employed zinc dimethyl and zinc diethyl to prepare the corresponding alkyls of silicon and many of the intermediate substitution products as well. The reactions were conducted in sealed tubes heated to about 160° and were of a straightforward metathetical type ... 

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,... 

In 1871, Ladenburg was the first to study the reaction of SnCl4 with a nonsymmetric tetraorganylstannane. As a result Et2SnCl2 and EtPhSnCl2 were obtained from Et3SnPh. 

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 ... 

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