1-Methyl-4-piperidone

Application

N-Methyl-4-piperidone can be used as a reactant to prepare:Spiropiperidine rings by reacting with malononitrile and electrophiles or Michael acceptors.(3E,5E)-1-Methyl-3,5-bis(phenylmethylene)-4-piperidinone by reacting with benzaldehyde via Michael addition, followed by intramolecular?O-cyclization/elimination sequential reactions.N,N′-Dimethylbispidinone by utilizing a double Mannich condensation method.

Preparation

[JACS (1948) vol 70 p 1820] for the synthesis of 1-methyl-4-piperidone: To a one-liter flask containing 350 ml of 20 % hydrochloric acid was added 86 g. of 1-methyl-3-carbethoxy-4-piperidone hyrdrochloride. After refluxing for one hour, the ferric chloride reagent gave no coloration. The solution was evaporated to dryness on a steam-bath at 10 mm. pressure. The solid product, heated at 100 °C for 4 hours at 0.1 mm and further dried over solid KOH for 24 hours, weighed 57.7 g, m.p. 80 - 120 °C.Although this melting range goes above that of the pure comound 0.45 of crude material dissolved in 90 ml. of hot acetone gave 0.40 g of pure compoundd melting at 93 - 95 °C. Other samples of crude piperidone hydrochloride showed even higher melting points than the one mentioned above, yet this apperently impure material always gave good yields of sharp melting product when recrystallized.

Purification Methods

It is best purified by fractional distillation The hydrochloride of the hydrate (4-diol) has m 94.7-95.5o, but the anhydrous hydrochloride which crystallises from CHCl3/Et2O has m 165-168o (164-167o) and can also be obtained by sublimation at 120o/2mm. The oxime has m 130-132o (from Me2CO). The methiodide crystallises from MeOH, the crystals with 1MeOH have m 189-190o, and the solvent-free iodide has m 202-204o(dec). [Lyle et al. J Org Chem 24 342 1959, Bowden & Greeen J Chem Soc 1164 1952, Tomita Yakugaku Zasshi (J Pharm Soc Japan) 71 1053 1951, Beilstein 21 IIII/IV 3183, 21/6 V 419.]