Reaction of trans-2-Acylaminocyclanols with Thionyl Chloride

Abstract

trans-2-Acetamidocyclohexanol (1; n = 2, R = CH,) on addition to thionyl chloride in chloroform at 0" was converted rapidly and quantitatively to D,L-2-methyl-4,5-cis-cyclohexanooxazoline hydrochloride (2; n = 2, R = CH,) judging from shifts in the methyl proton resonances of the n.m.r. spectra of the amide and the reaction solution. The intermediate chlorosulfinate was estimated to have a half-life of less than 2.25 min. The oxazoline salt was isolated in 98% yield by sublimation of the crude product in vacuo and was identified by its i.r. and n.m.r. spectra and by its facile and almost quantitative hydrolysis to cis-2-aminocyclohexanol hydrochloride. The oxazoline salts 2 (n = 1, R = CH3, C6H4-pN02 and n = 2, R = C6H5, C6H4-pNO2) were readily obtained in 95% yield or better by the same general method and it was shown that the trans-2-acetamidocyclanols are the preferred starting materials for conversion to cis-2-aminocyclanol derivatives by the thionyl chloride inversion reaction. The oxazoline bases 4 (n = 1, R = CH,, C6H4-pN02 and n = 2, R = CH,, C6H4-pNO2) were readily obtained in high yield from the corresponding salts and differences in the i.r. and n.m.r. spectral characteristics of the salts and bases are reported.La D,L-mtthyl-2 cyclohexano-4,5-cis oxazoline (2; n = 2, R = CH3) est rapidement et quantitativement produite en ajoutant le chlorure de thionyle & 0 "C A I'acttamido-2 cyclohexanol-tram (1; n = 2, R = CH,) dans du chloroforme. On estime que le demi temps de vie du chlorosulfinate intermtdiaire est moins que 2.25 min. Ce rtsultat est mis en Bvidence par un glissement dans le signal des protons du groupement mtthyle dans les spectres r.m.n., de I'amide et de la solution rtactionnelle. Le chlorhydrate de I'oxazoline est isolt avec un rendement de 98% par la sublimation sous vide du psoduit brut. On a Btabli la structure du compod en se servant de donntes obtenues par spectroscopie i.r. et r.m.n. et on I'a vkrifite par une mtthode d'hydrolyse simple qui conduit avec un rendement pratiquement quantitatif au chlorhydrate de I'amino-2 cyclohexanol-cis. On obtient facilement les chlorohydrates des oxazolines 2 (n = 1, R = CH,, C6H4-pNO2 et n = 2, R = C6H,, C6H4-pNO2) avec des rendements d'au moins 95% en utilisant la mkme mtthode gCntrale et on a ddmontrt que les acttamido-2 cyclanols-trans sont les produits de dtpart les plus utiles pour obtenir les dBrivts d'aminocyclanol-2-cis par la rtaction d'inversion & l'aide du chlorure de thionyle. On obtient facilement les bases oxazolines 4 (n = 1, R = CH,, C6H4-pNO2 et n = 2, R = CH3, C6H4-pN02) avec de bons rendements & partir des sels correspondants et on dkrit des diffkrences dans les spectres r.m.n. et i.r. des sels et des bases.

Application of photoelectron spectroscopy to intramolecularly hydrogen-bonded systems. Part III. The photoelectron spectra of cis and trans 2-substituted cyclopentanols and cis and trans 2-substituted cyclohexanols

“…(7). Methylation of the cis isomer by the Eschweiller-Clarke procedure (8) afforded cis-2-(N,N-dimethylamino)cyclohexanol while the corresponding tr.atls isomer was produced by opening of cyclohexene oxide with dimethylamine (9).…”

Enantioselective synthesis of heterocyclic compounds mediated by organoselenium reagents

“…Using a method described in the literature 18 the trans oxazolines 26 can be converted into cis oxazolines 29 by ring opening with dilute hydrochloric acid to give 27 and transformation of the OH group into the chlorosulfite 28 which can suffer intramolecular substitution with inversion of configuration at the carbon atom. Thus, all the possible four stereoisomers of 4,5-bis-substituted oxazolines could be obtained in an enantiomerically pure form.…”

Substituent Interactions in Di- and Tri-acyl Derivatives of cis- and trans- 2-Hydrazinocyclopentanol

“…The conversion of 5 into 3 is in fact an example of a well established reaction type in which an a-acylamino alcohol is transformed by acidic reagents (most frequently thionyl chloride) into a derivative of the amino alcohol with inversion at the carbinol carbon (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). The key step is the formation of an oxazolinium cation by S,2 attack of the acylamino oxygen.'…”

“…These have been isolated as the free bases, (e.g. 6 from trans-2-benzoylaminocyclohexanol) which are usually stable, or as their salts (3)(4)(5)(7)(8)(9)(10). Hydrolysis of the oxazolines by acids gives the cis-2-acyloxycycloalkylamines (C-N cleavage, overall N + 0 migration) (2,4, 7, 8, lo), or, if prolonged, the cis-alcohols themselves (3, 5-8, lo), while hydrolysis by basic reagents appears to give cis-2-acylaminocycloalkanoIs (C-0 cleavage) (8,9).…”