Octahydroacridines

A highly diasteieoselective synthesis of substituted 1,2,3,4,4a,9,9a, 10-octahydroacridines 95 with five stereogenic centers has been achieved by domino imine condensation/intramolecular polar [4ti + 2k] cycloaddition of anilines and oo-unsaturated aldehydes 94 <96JPR(338)468>. 

Interesting octahydroacridines 2-860 have been prepared by Beifuss and coworkers by combining the condensation step with a rare intramolecular polar [4jt++2 jrj-cydization of a-aryliminium ions 2-859, obtained from anilines 2-857 by reaction with the oo-unsaturated aldehyde 2-858 (Scheme 2.191) [440]. The overall domino process seems to be stereoselective, since the formation of the two di-astereomers 2-860 can be traced to the use of the substrate 2-858 as a diastereom-eric mixture. 

Scheme 2.191. Domino condensation/cycloaddition reaction leading to octahydroacridine 2-860.

Benzo ring reduction in acridine can be achieved in a variety of ways. 1,4,5,8-Tetrahydro-acridine is given by lithium in liquid ammonia and ethanol (Scheme 35) (69AJC1105). The symmetrical octahydroacridine (48) can be obtained by hydrogenation of acridine over platinum oxide in trifluoroacetic acid. The product is obtained in quantitative yield (Scheme... 

B. 9-n-Butyl-1,2,3,4,5,6,7,8-octahydroacridine. A 1-L, three-necked, round-bottomed flask equipped with a mechanical stirrer, glass stopper, and a reflux condenser fitted with a nitrogen gas inlet tube which is attached to a mineral oil bubbler is flushed with nitrogen and then charged with 17.0 g (0.22 mol) of ammonium... 

L, round-bottomed flask equipped with a magnetic stirrer, reflux condenser, and a 250-mL addition funnel are placed 56.3 g (0.26 mol) of MCPBA (80%) and 350 mL of dichloromethane. The suspension is stirred and a solution of 38.0 g (0.16 mol) of 9-n-butyl-1,2,3,4,5,6,7,8-octahydroacridine in 120 mLof dichloromethane is added rapidly (exotherm). When the reaction mixture ceases to boil gently from the heat of reaction, it is heated to extend the reflux period to a total of 2.5 hr. The reaction mixture is cooled to room temperature, extracted with 0.5 M aqueous sodium hydroxide (4 x 450 mL), and dried over anhydrous sodium sulfate. The drying agent is removed by filtration, the filtrate is concentrated with a rotary evaporator, and the residual solvent is removed at 0.1 mm pressure to afford 40 g (99%) of yellow crystalline product, mp 96-100°C. 

Taken together, Steps A and B of this procedure describe the most expedient, large scale approach to 9-n-butyl-1,2,3,4,5,6,7,8-octahydroacridine, which is prepared in about 60% overall yield from inexpensive starting materials. This heterocycle is an important building block for hexagonal lattice receptors, which are relatively rigid, planar hosts for metal ions and organic molecules.2... 

The volume concludes with three convenient procedures to make functionalized molecules having varied applications 5,6-DIETHOXYBENZOFURAN-4,7-DIONE, 9-n-BUTYL-1,2,3,4,5,6,7,8-OCTAHYDROACRIDIN-4-OL, and ETHYL 3,3-DIETHOXYPROPANOATE. 

Diels-Alder reactions are a very versatile means of synthesizing several ring systems in a single-step process. This protocol has been used to form octahydroacridine derivatives by taking A-arylimines which contain a nonactivated alkene functionality appropriately... 

Reaction of the lactol 1 with the isocyanate 2 in acetonitrile in the presence of 5 mol % of DBU resulted in a cascade of reactions and formation of a pentacyclic product A in 86% yield. Treatment of A with methoxide gave the highly functionalised octahydroacridine 3 in 90% yield. 

In a similar approach the condensation of aniline 234 with simple aliphatic aldehydes 233 containing a dienophile moiety in the presence of the Lewis acid SnCl4 led to octahydroacridine 236 in high trans-selectivity, if R1 and R2 are methyl groups (Scheme 5.46) [62],... 

Schulte, J. L. Laschat, S. Kotila, S. Hecht, J. Frohlich, R. Wibbeling, B. Synthesis of j 6-(octahydroacridine)chromiumtricarbonyl complexes with non-polar tails via molecular sieves-catalyzed cydization of N-arylimines and subsequent diastereoselective complexa-tion. Heterocydes 1996, 43, 2713-2724. 

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