1 - piperidine alkoxylation

These factors are sufficient to produce similar amounts of aminated isomers from 2,4-dichloropyrimidine which gives predominantly 4-alkoxylation products. Thus, a mixture of 2-amino-4-chloro- (302) and 4-amino-2-chloro-pyrimidine (303) is obtained on treatment of 2,4-dichloropyrimidine with alcoholic ammonia (25°, <18 hr), the reagent here being better at hydrogen bonding than piperidine. 

The rate of amination and of alkoxylation increases 1.5-3-fold for a 10° rise in the temperature of reaction for naphthalenes (Table X, lines 1, 2, 7 and 8), quinolines, isoquinolines, l-halo-2-nitro-naphthalenes, and diazanaphthalenes. The relation of reactivity can vary or be reversed, depending on the temperature at which rates are mathematically or experimentally compared (cf. naphthalene discussion above and Section III,A, 1). For example, the rate ratio of piperidination of 4-chloroquinazoline to that of 1-chloroisoquino-line varies 100-fold over a relatively small temperature range 10 at 20°, and 10 at 100°. The ratio of rates of ethoxylation of 2-chloro-pyridine and 3-chloroisoquinoline is 9 at 140° and 180 at 20°. Comparison of 2-chloro-with 4-chloro-quinoline gives a ratio of 2.1 at 90° and 0.97 at 20° the ratio for 4-chloro-quinoline and -cinnoline is 3200 at 60° and 7300 at 20° and piperidination of 2-chloroquinoline vs. 1-chloroisoquinoline has a rate ratio of 1.0 at 110° and 1.7 at 20°. The change in the rate ratio with temperature will depend on the difference in the heats of activation of the two reactions (Section III,A,1). 

Intramolecular electrochemical alkoxylation of racemic l-(3-hydroxybu-tyryl)piperidine afforded a diastereomeric mixture of 2-methylperhydropyr-ido[2,l-Z)][l,3]oxazin-4-ones (OOMIl 1). 

Tetrahydropyran, like piperidine, adopts a chair conformation. One of the interesting aspects to emerge from studies of alkoxy-substituted tetrahydropyrans is that when located at C-2, alkoxyl groups prefer an axial orientation (the anomeric effect °). The reason for this is that in an equatorial orientation there are unfavourable dipole-dipole interactions between lone pairs on the two oxygen atoms, and the energy gain, when these are relieved in a conformation with the C-2-substituent axial, more than offsets the unfavourable 1,3-diaxial interactions which are introduced at the same time. 

N-4-Ghlorotetrafluorophenylpiperidine N-oxide allowed to react at room temp, with dimethylamine in dioxane -> N-(4-chloro-2,6-dimethylamino-3,5-difluoro)-piperidine N-oxide. Y 90%. F. e., also 4-substitution by alkoxyl, s. M. Bellas and H. Suschitzky, Ghem. Commun. 1965, 367. 

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