Atropisomeric 8,8-biquinolyl derivatives: Synthesis, properties and applications. Selena D. Milicevic

ISBN: 9780549710837

Published:

NOOKstudy eTextbook

654 pages


Description

Atropisomeric 8,8-biquinolyl derivatives: Synthesis, properties and applications.  by  Selena D. Milicevic

Atropisomeric 8,8-biquinolyl derivatives: Synthesis, properties and applications. by Selena D. Milicevic
| NOOKstudy eTextbook | PDF, EPUB, FB2, DjVu, AUDIO, mp3, RTF | 654 pages | ISBN: 9780549710837 | 5.23 Mb

7,7-Dihydroxy-8,8-biquinolyl (azaBINOL) was prepared from 7-hydroxyquinoline via N,N-dimethyl O-quinol-7-yl carbamate by directed ortho-metallation followed by FeCl3-mediated oxidative coupling of the 8-lithioquinoline intermediate. SaponificationMore7,7-Dihydroxy-8,8-biquinolyl (azaBINOL) was prepared from 7-hydroxyquinoline via N,N-dimethyl O-quinol-7-yl carbamate by directed ortho-metallation followed by FeCl3-mediated oxidative coupling of the 8-lithioquinoline intermediate.

Saponification of the resulting dicarbamate provided crystalline (+/-)-azaBINOL in 56% overall yield. 6,6-Bis(dimethylaminocarbonyl)-7,7-dihydroxy-8,8-biquinolyl was prepared from the same dicarbamate by a double anionic-Fries rearrangement in 43% yield.

7,7-Bis(diethylamino-carbonyloxy)-6,6-diiodo-8,8-biquinolyl was synthesized from 7-(diethylaminocarbonyloxy)-8-iodoquinoline in 54% yield by a tandem halogen-dance/oxidative coupling process. The diiodide was converted to 6,6-bis[(methylamino)-sulfonyl]-7,7-dihydroxy-8,8-biquinolyl by a three-step sequence in 91% overall yield.-Resolution of (+/-)-azaBINOL into its atropisomeric enantiomorphs was accomplished in two ways: (a) via chromatographic (HPLC) separation of diastereomeric bismenthylcarbonates generated from the racemic diol and homochiral menthylchloroformate, and (b) via hydrolytic enzymatic kinetic resolution of the (+/-)-azaBINOL dipentanoate ester derivative with bovine pancreas acetone powder.

Method (b) was superior and afforded the unreacted (+)-( aR)-diester (46%, ≥99%ee) accompanied by (--)-(aS )-azaBINOL (30%, 92%ee after recrystallization). 2,2-Di- tert-butyl-azaBINOL was prepared in enantioenriched form from scalemic samples of azaBINOL-dipentanoate by addition of t-BuLi followed by saponification in the presence of air.

First-order rate constants for the enantiomerization of azaBINOL in H2O were measured (over 316--366 K) and activation parameters determined as DeltaH‡ = 34.0 kcal mol-1 and DeltaS‡ = 18.7 cal mol-1 K-1 by Eyring plot analysis. The further functionalized 2,2-di-tert-butyl-azaBINOL was found to be configurationally labile and showed racemization half-lives of 30.5 h and 1.9 h at 23°C in MeOH and CHCl3, respectively.-A series of cyclic diethers were prepared from azaBINOLs and dihalides X(CH2)nX (n = 1--6) and their pKa values determined by potentiometric titration in MeOH.

Biquinolyl basicity was dependent on interannular dihedral angle (IDA- assessed by X-ray crystallography and UV spectroscopy), the methylene diethers (IDA ≤60°) exhibited single pKa points of exceptionally low magnitude (2.7--3.1).-6,6-Bis[(methylamino)sulfonyl]-7,7-dihydroxy-8,8-biquinolyl, resolved via an HPLC based method, catalyzed the enantioselective addition of TMSCN to aldehydes in the absence of additives.

Resulting cyanohydrins were obtained in ≥ 90% yield and up to 20%ee. Control experiments established the requirement of sulfonamide functionality, free hydroxyl groups, quinoline nitrogen atoms and the dimeric manifold for catalytic activity.



Enter the sum





Related Archive Books



Related Books


Comments

Comments for "Atropisomeric 8,8-biquinolyl derivatives: Synthesis, properties and applications.":


thefungiforager.com

©2008-2015 | DMCA | Contact us