Dehydrogenation of piperidine

Dehydrogenation of piperidine derivative 329 with Hg(II)-EDTA reagent afforded a mixture of perhydropyrido[l,2-n]pyrimidin-2-one 330 and pyrido[],2-c][],2,5]oxadiazine 331 (99ZN(B)632). 

An interesting application of heteroaromatic (V-imines involves dehydrogenation of piperidine, anabasine, and Hantzsch ester.266-269... 

Activation Energies of Dehydrogenation of Piperidine, Cyclohexane and Decalin Metals of Various Atomic Radii Atomic radius Piperidine Cyclohexane Decalin ... 

A large number of pyridine derivatives have been obtained by the dehydrogenation of suitable piperidines. 

Tetra- and hexa-hydro compounds can often be aromatized, but this is more difficult than in the corresponding dihydro series. Thus, the conversion of piperidines to pyridines typically requires dehydrogenation with Pd at 250°C. 

The reaction of piperidine conjugated dehydrogenation with hydrogen peroxide [99] opens the way to dehydrogenation of natural compounds, which include piperidine fragments. As shown by experimental data, pyridine yield increases from 45% to 65.2% with hydrogen peroxide concentration from 20% to 25%, respectively, with reaction selectivity above 98%. A further increase of H202 concentration reduces pyridine yield to 59%. It follows from these... 

The iV-alkylation was considered to occur by the reaction of the carbonyl compounds, formed by the dehydrogenation of alcohols over the catalyst, with the hydrogenation products of pyridine,25 as suggested by Schwoegler and Adkins, who obtained good yields of /V-alkylpiperidines by the reaction of piperidine with alcohols.26 Maruoka et al. obtained a higher maximal yield of the iV-ethylated product in ethanol over Raney Co than over Raney Ni in the hydrogenation of 5-ethyl-2-methylpyridine (eq. 12.16),23 an alkylated pyridine prepared industrially by the reaction of acetaldehyde with ammonia. 

Representative compounds having a pyrrolidine or piperidine nucleus have been dehydrogenated in benzene solution under pressure at 250-350° over a nickel catalyst, e.g., l-( -amyl)-pyrrolidine to l-( -aniyl)-pyrrole (88%), indoline to indole (75%), and 1,2,3,4-tetrahydrocarbazole to carbazole (95%). Indole is also prepared by the dehydrogenation of its 2,3-dihydro derivative over palladium in boiling xylene (62%)." Partially hydrogenated alkylpyridines are dehydrogenated over palladized asbestos." 2,4-Diphenylpyrrole is synthesized by the selenium dehydrogenation of its 2,3-dihydro compound (46%). ... 

A mixture of lupinine and epilupinine is obtainable by the following series of reactions. The betaine XXVI on cyclic hydrogenation and subsequent decarboxylation with 20 % hydrochloric acid gives a mixture of epimeric lupininic acids (XXIX). The dicarboxylic ester XXVIII is also obtained by the mercuric acetate dehydrogenation of the piperidine derivative XXX and by the alkylation of monomeric piperideine with a y-bromopropylmalonic ester. The last route is presumably a first Mannich condensation followed by an alkylation. Hydrolysis of the malonic esters, decarboxylation (XXIV), esterification, and reduction with lithium aluminum hydride complete the synthesis of a mixture which consists of 80% dZ-epilupinine and 20% dMupinine. Thermal... 

Dehydrogenation of himbacine with palladium-charcoal at 260° furnished dehydrohimbacine (V). That the transformation involved the saturation of the double bond and the conversion of an A -methyl-piperidine system into a pyridine derivative was apparent from the elemental analysis of the product, its UV-spectrum 265 mp, log 3.65), and the marked change in p/v from 9.3 to 5.4 (50% ethanol). Compound V was also obtained from dihydrohimbacine under the same conditions. 

Dehydrogenation of himandravine by palladium-charcoal gave de-hydrohimbacine (V) in good yield. The structure of the alkaloid therefore differed from that of himbeline merely by having a different configuration at one or both of the asymmetric carbon atoms of the piperidine ring (2). 

The piperidine and quinolizidine enamines and enamines of l-azabicyclo[4.3.0]-nonane, l-azabicydo[5.3.0]decane, l-azabicyclo[5.4.0]undecane and 1-azabicyclo-[5.5.0]dodecane have been prepared in this manner . The dehydrogenation of 4-aryIquinolizidines is interesting since the double bond of the salts is formed in the A -position and not in the expected "-position . In several cases, hydroxylation takes place. Examples are the dehydrogenation of 1-methylquinolizidine and of cis- and rra i-l-methyldecahydroquinoiines (equation 22). 

The most accepted biosynthetic pathways for piperidine is lysine via A -piperidine (3973, 17B05). Piperidine can also be formed through decarboxylation and dehydrogenation of nicotinic acid (17B37). 

To show the way in which one of the piperidine isomers was synthesized and how each was utilized to make heteroyohimbine alkaloids, the full synthesis of ( )-tetrahydroalstonine (44a) and ( )-akuammigine (44b) is detailed in Scheme 11. As well as the effective dehydrogenation of the ethyl group, notable in the sequence is the intramolecular oxymercuration, (45) — (46), which in the cis-series leads, by kinetic control, only to the 19 -isomer. Also of interest is the absence, apparently, of inside isomers (such as have been reported in other similar cyclizations, see below) in the closure of the C-ring, i.e. (47) — (44). 

Piperidine Derivatives. Dehydrogenation of both l-methyl-3-(2-hydroxy-ethyl)- and -(3-hydroxypropyl)-piperidines (351) with mercuric ion and edta... 

Ring expansion of ftve-membered ring heterocycHc compounds has been accompHshed to form pyridine derivatives. Reaction of tetrahydrofurfuryl alcohol with ammonia gives pyridine (1) under dehydrogenating conditions, and gives piperidine (18) under reductive conditions. 

Aldoximes can be oxidatively dehydrogenated to nitrile oxides using a variety of oxidants such as lead tetraacetate [16a], alkali hypohalites [lla],NBS in DMF followed by base treatment [16b], chloramine-T [11b], 1-chlorobenzotriazole [16c], mercuric acetate [ 16 d], etc. However, we employed either NaOCl or chloramine-T for most of our INOC reactions. For instance, a piperidine ring fused to an isoxazoline as in 14 was constructed using the INOC methodology (Scheme 3) [17]. Monoalkylation of N-tosylallylamine 10 with the bromoacetal... 

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