Phenylpiperidine

Submitted by A. N. Bourns, H. W. Embleton, and Mary K. Hansuld.1 Checked by R. T. Arnold, William E. Parham, and Carl Serres. 

The apparatus (Fig. 4) consists of a reaction tube, 100 cm. long and 3 cm. in diameter, provided with an inlet tube to which a graduated dropping funnel is connected. The lower end of the 

The catalyst employed was Alcoa Activated Alumina (Grade F-l, 4- to 8-mesh) from the Aluminum Company of America. A fresh catalyst is brought to a condition of maximum activity by passing a slow stream of air through the catalyst bed for 94 hours at 390-405°. Without this pretreatment, yields are 5-10% lower than those reported here. The catalyst is reactivated after each run by passing air through it for 39 hours at 390-405°. 

The furnace may be of the construction described in a previous volume. It is desirable, although not essential, to 

The temperature of the furnace is measured by a thermocouple which can be moved to various positions in the thermocouple well. The catalyst temperature should be maintained at 325-345°, although it may be as low as 320° at the ends of the catalyst zone, depending unon the construction of the furnace. 

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Reduction of o /i-unsatin-ated lactams, S,6-dihydro-2-pyridones, with lithium aluminum hydride, lithium alkoxyaluminum hydrides and alane gave the corresponding piperidines. 5-Methyl-5,6-dihydro-2-pyridone (with no substituent on nitrogen) gave on reduction with lithium aluminum hydride in tetrahydrofuran only 9% yield of 2-methylpiperidine, but l,6-dimethyl-5,6-dihydro-2-pyridone and 6-methyl-l-phenyl-5,6-dihydro-2-pyridone afforded 1,2-dimethylpiperidine and 2-methyl-1-phenylpiperidine in respective yields of 47% and 65% with an excess of lithium aluminum hydride, and 91% and 92% with alane generated from lithium aluminum hydride and aluminum chloride in ether. Lithium mono-, di- and triethoxyaluminum hydrides also gave satisfactory yields (45-84%) [7752]. 

Phenylpiperidine has been prepared by warming aniline with 1,5-dibromopentane 4,8 heating 5-anilino-l-bromopentane 6 the dehydration of 5-anilino-l-pentanol over alumina 7 the electrolytic reduction of N-phenylglutarimide 8 the catalytic hydrogenation of l-phenyl-3-hydroxypyridinium chloride 9 the action of bromobenzene on piperidine in the presence of lithium 10 the reaction of fluorobenzene, 1-methylpiperidine, and phenyl-lithium 11 the action of diphenylsulfone on piperidine in the presence of sodamide 12 the diazotization and deamination of l-(2-aminophenyl)piperidine 13 and of l-(4-aminophenyl)piperidine 14 and the present method.18... 

Phenylpiperidine reacts with fuming nitric acid (d 1.5) at -10°C to produce about 90% l-(2,4-dinitrophenyl)piperidine. Mononitration can be achieved by using nitric acid in acetic anhydride at RT, which gives the 4-nitrophenyl product in quantitative yield with no ortho product to be seen. The 4-nitrophenyl product is nitrated by concentrated nitric acid (d 1.42) to give the 2,4-dinitropheny 1 compound, but the 2-nitrophenyl isomer (prepared from piperidine and 2-nitrochlorobenzene) is unaffected even by fuming nitric acid (32JCS1376). 

A temperature of 330-340° and use of an aluminum oxide catalyst are necessary for conversion of tetrahydropyran into 1-phenylpiperidine by means of aniline 1105 tetrahydro-furan gives pyrrolidine under similar conditions.1106... 

Phenylpiperidine, 34, 79 Phenylsuccinic acid, 30, 83 Phenylsuccinic anhydride, 30, 85 Phenylthiourea, 31, 22 Phenyl -tolyl sulfone, 32, 10 7-Phenylvaleric acid, 36, 97... 

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