Studies of Hydrogen Bonding. III. Intramolecular Hydrogen Bonding in 3-Piperidinols

Abstract

HYDROGEN BONDIPI'G IN 3-PIPERIDINOLS 1207were vacuum distilled from the residue. The remaining material was dissolved in 3 ml. of benzene and treated with 520 mg. (0.002 mole) of stannic chloride. After 1 hour a t ordinary temperature, the mixture was diluted with ether and extracted successively with 2 N aqueous hydrochloric acid, 2 N aqueous potassium hydroxide and water. The remainder from the dried (MgSOa) ether solution was recrystallized from a mixture of ethanol and water: vield 34 mg. (107'); infrared spectrum: 6.10 p (carbonyl associated with NH); m.p. 250-252°.32 Calcd. for CllHgSO (171.19): C, 77.17; H, 5.30. Found: C, 77.04; H, 5.66.Anal.Diethyl a,a-di-(4-cyanoskatyl)-malonate was isolated from the mother liquors remaining after the crystallization of ethyl a-carboethoxy-~-(4-cyano-3-indole)-propionate1 and was purified by recrystallization from acetone; m.p. 235-237".Anal. Calcd. for CnH24N204 (440.48): C, 69.22; H, 516; N, 11.96. Found: C, 69.10; H, 5.50: N, 11..97.Methyl (4-Carbomethoxy-3-indole)-acetate.-To a solution of 200 mg. (0.001 mole) of 4-cyanogramine and 326 mg. (0.005 mole) of potassium cyanide in 25 ml. of methanol was added, in 4 portions a t 15-minute intervals, 2.0 ml. (0.02 mole) of dimethyl sulfate. After 3 hours a t ordinary tem-(32) Cf. the preparation of this substance by the Fischer procedure from 1,2-cyclopentadione monophenylhydrazone: R . H. F. hlanske, Can.

1‐Arylquinolizidines

“…Epimers 9a-e showed broad hytlroxyl absorption with maxima occurring a t variable wavc riunibws (;UOO c~-' -3480 crn-') in the infrared spc:c,tra ('J'able 11). This is in good agreement with the position of iritramo1t:c:ularly hydrogen bonded 0--H stretch rc:portc:d by othcrs (6,7).…”

A thermodynamic study of ketoreductase-catalyzed reactions 5. Reduction of substituted ketones in n-hexane

“…Using these computational results, the substance 3-hydroxypiperidine is found to have a calculated standard molar enthalpy of formation D f H m (from total energy + thermal correction) that is 6.1 kJ AE mol À1 more negative than 4-hydroxypiperidine and a standard molar Gibbs free energy of formation D f G m that is 4.9 kJ AE mol À1 more negative. These results are consistent with the hydrogen bond suggested spectroscopically for the 3-isomer [36] and the resultant stabilization and the seeming absence of such stabilization for the 4-isomer [37]. However, it is not consistent with the calorimetrically determined standard molar enthalpies of formation [32].…”

Associated XH Frequencies, the Hydrogen Bond

“…They note that hydrogen bonding does not occur if the bond to a substituent is inclined at an angle greater than 60° to the C-C axis. Other useful papers on this topic are those ofHite et al [134] (3piperidinols), De Roos and Bakker [135] (amino alcohols of trihexyphenidyl*), Igonin and Bass [136] (hydroxy benzylamines) and of Freedman [129]. Other useful papers on this topic are those ofHite et al [134] (3piperidinols), De Roos and Bakker [135] (amino alcohols of trihexyphenidyl*), Igonin and Bass [136] (hydroxy benzylamines) and of Freedman [129].…”