1.5- diazabicyclo nonanes

C]()Hi,N02S 3054-01-1) see Bucillamine ( )-cis-8-benzyl-2,8-diazabicyclo[4.3.0]nonane (C14H20N2 161594-54-3) see Moxifloxacin hydrochloride... 

Aliphatic amines, which are hard bases, are unfavorable for coordination to soft Ni°. If the principles of ligand preorganization and donor prepositioning are applied, however, (diamine)Ni° complexes are accessible, which has been demonstrated for complex (1020) with a rigid N,N -dimethyl-3,7-diazabicyclo[3.3.1 ]nonane ligand.2468... 

The final step to 46 is cyclocondensation of 3,7-diazabicyclo[3.3.1]nonane (51), bispidine70, with formaldehyde. There are two different approaches to 51 (i) a pyridine is converted to a piperidine and (ii) the double Mannich or Robinson-Schopf condensation of ketone 52 with formaldehyde and primary amines affords 1,5-disubstituted 3,7-dazabicyclo[3.3.1]nonan-9-one (53), bispidone, from which 5,7-disubstituted l,3-diazaadamantan-6-one (61) is derived. Route (i) is adopted by Galinovsky and Langer,71 Stetter and... 

Isomeric l,3-diaza-6-thiaadamantane 6,6-dioxide (232) is prepared by cyclocondensation of 3-benzenesulfonyl-9-thia-3,7-diazabicyclo[3.3.1]nonane-9,9-dioxide (233) with formaldehyde, where 233 is derived from /V-benzene-sulfonyl-2,6-dimethylthiomorpholine (234).2 54... 

A similar vinylogous Mannich reaction has been used by Martin in the total syntheses of the heteroyohimboid alkaloids (—)-ajmalicine and (—)-tetrahydroalstonine <1995JOC3236>. An attempted synthesis of an opioid analgesic 2,4-dibenzyl-3,7-diazabicyclo[3.3.1]nonan-9-one-l,5-dicarboxylate (piperidone) by a double Mannich reaction of oxoglutarate, 2 equiv of phenylacetaldehyde, and methylamine did not give the expected product but instead gave rise to an unexpected [l,6]naphthyridine derivative (Scheme 57) <1998PHA442>. 

Beckmann rearrangement of quinuclidin-3-one oxime (103) in the presence of polyphosphoric acid or oleum proceeds with quinuelidine ring expansion and the formation of 3-oxo-l,4-diazabicyclo[3.2.2]-nonane (146).m,m... 

Figure 10. Ni(II) complex of the bispidine-based hexadentate ligand L8 (bispidine= 3,7-diazabicyclo[3.3.1]nonane) with the corresponding cavity size function, i.e. the strain energy as a function of the averaged metal donor distances.78...

An older paper <1971MI873> reported that ozonolysis of alkenes in the presence of tertiary amines resulted in the formation of aldehydes. A recent reinvestigation <20060L3199> has shown that amine oxides were responsible for this reductive ozonolysis . Indeed, pretreatment of the tertiary amines with ozone, giving rise to amine oxides, accounted for this phenomenon. A preparative method emerged, by treating the alkene (e.g., 1-decene) at 0 °C with a solution of 2% 03/02 in dichloromethane (2 equiv of ozone relative to the alkene) in the presence of an excess (about threefold molar excess) of A-methylmorpholine A-oxide, pyridine A-oxide, or l,4-diazabicyclo[2.2.2]octane A-oxide (DABCO A-oxide). Yields of aldehydes (nonanal in the above example) were 80-96%, and the excess of amine oxide ensured the absence of residual ozonide (Scheme 21). 

A mixture of l-cyclopropyl-6,7-difluoro-l,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid, 2,8-diazabicyclo[4.3.0]nonane, DBU (1,8-diazobicyclo[5.4.-0]undec-7-ene and anhydrous acetonitrile was refluxed. 

The enantiomerically pure amines 82 and 84 are for example prepared by resolution of the racemic 8-benzyl-rfs-2,8-diazabicyclo[4.3.0]nonane 79 using natural R,R(+)-tartaric acid, whereupon the diastereomerically pure i ,i -tartrate of the R, /<-enantiomer is crystallized from dimethylformamide (DMF) and can be purified by recrystallization from methoxyethanol. The target S,S-enantiomer contained in the mother liquor is first converted into the free base, which is then, for the purpose of further purification, precipitated with S,S(-)-tartaric add to give the diastereomerically pure S,S-tartrate. The S,S-enantiomer 83 is then liberated with sodium hydroxide solution. The R,R-enantiomer 81 is obtained in the same way. Separation of the enantiomers can also be carried out with high optical yields in an aqueous/alcoholic solution [140]. The hydrogenolytic debenzylation of 81 and 83 produces the corresponding pure R,R- and, S, S —2,8-diazabicyclo[4.3,0]no-nanes 82 and 84 (Scheme 14.2) [129]. 

An enzymatic method for resolution of the racemic cis-2,8-diazabicyclo[4.3.0[-nonane has also been described, in which reaction of the S,S-enantiomer with ethyl acetate in the presence of lipase produces the S,S-diacetyl derivative under the reaction conditions and the R, K-eriari liorner is only reacted to form the monoacetyl derivative. The components can be readily separated from the resulting reaction mixture, and then deacetylated [141]. 

Scheme 14.2 The synthesis of enantiomerically pure 2,8-diazabicyclo[4.3.0]nonanes.

N-Alkyl and N-Acyl Derivatives of 3,7-Diazabicyclo-[3.3.1] Nonanes and Selected Salts Thereof as Multiclass Antirrhythmic Agents... 

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