Crystal structure of (1S,2R,4S,5S)-5-ethynyl-2-hydroxymethyl-1-azabicyclo[2.2.2]octane, (HC2)(HOCH2)C7H11N)

Abstract

Source of materialQuincoridine® [1] (2.0 g, 12 mmol) was dissolved in dry CCI4 (15 ml). Bromine (1.1 ml, 21.5 mmol) was added at 273 Κ. The reaction mixture was stirred for lh. After removal of the solvent in vacuo the resulting yellow solid was dissolved in CHCI3 (25 ml). Et3N (3.1 ml, 24 mmol) was added and the mixture was then stirred for 4h at RT. After work-up (CHCI3 and saturated aqueous solution NaHC03) the vinylic bromide (0.2 g, 0.81 mmol) was dissolved in THF (10 ml), followed by addition of powdered KOH (116 mg, 2.0 mmol) and aliquat 336® (0.73 ml, 0.16 mmol). The reaction mixture was heated at reflux for 7 h. Work-up (CHCI3 and saturated aqueous solution NaHCOs) and column chromatography (ethyl acetate / methanol 6:1) furnished the title compound which crystallized after 5 h at 273 K. The compound melts at 317 Κ and sublimes readily. DiscussionThe title compound 1 is derived from quinidine [2] via quincoridine® (QCD) [1,3,4] and is to be compared to the (lS,2S,4S,5S)-diastereomer 2 which is derived from quinine [5] via quincorine® (QCI) [1,3,4], The transformation of QCD and QCI to compounds 1 and 2, respectively, can formally be described as the replacement of the vinyl group by the ethynyl group (see scheme 1 in [6]). Compound 1 is called 10,11-didehydroquincoridine and compound 2 10,11-didehydro-quincorine [6]. In view of the high synthetic flexibility of alkynes we expect that 1 and 2 will become valuable homochiral building blocks, e.g. in asymmetric synthesis and in medicinal chemistry, similar to QCD and QCI [3,4,7]. The terminal alkynes 1 and 2 have the advantage of being solids at room temperature, while QCD and QCI are liquids. The crystal structure of 2 has already been reported inThe X-ray analysis of 1 (this work) shows that its crystal packing has the higher point group symmetry (222 instead of 2) but the lower density by about 2 %. In the solid state the molecules of compound 1 are connected to helical chains by hydrogen bonds in a similar manner as found in compound 2 (see the figure in [8]) and in quinidine [2]. The chain direction in 1 is [100] and corresponds to the [010] direction in 2. Substituted quinuclidines are often twisted [9]. The dihedral angles C2-N1-C4-C3, C6-N1-C4-C5 and C7-N1-C4-C8 are 10.9°, 9.7° and 9.1°, respectively, with an average of 9.9° for molecule 1 and 3.7°, 6.7°

Crystal and molecular structures of new enantiopure quinuclidines

“…The bond lengths and bond angles in both cation and anion agree within 3s with the values observed in the structures of quinidine 10 and didehydroquincoridine 11 as well as in hydrogen-(R,R)-tartrate. 12 …”

Crystal structure of (1S,2R,4S)-2-bromomethyl-1-azabicyclo[2.2.2]·octan-5-one, C8H12BrNO

“…(15,2if,45)-2-Bromomethyl-l-azabicyclo[2.2.2]-octan-5-one contains a prochiral carbonyl group and three stereogenic centres including the chiral 5-configurated bridgehead nitrogen. The analysis of N,C-bond angles shows a less developed pyramidalization of the bridgehead nitrogen than in 10,11-didehydroquincorine and -quincoridine [8,9,10]. …”

Photoelectron Spectra and Electronic Structure of Some Diastereomeric Quinuclidine Derivatives

“…In Table 1 the torsion angles of 5 [11] and 6 [12] from X-ray analyses have been included for comparison. While for compound 5 the calculated distortion of the bicycle corresponds well to the experimental result, for compound 6 the three corresponding torsion angles have the opposite sign, indicating that in the crystalline state the molecule should have a similar distortion as 5.…”