8- Azabicyclo octan-3-one

A new class of bicyclic oxalactam, 8-oxa-6-azabicyclo[3.2.1]octan-7-one 61 was synthesized by intramolecular cyclization of 3,4-dihydro-2H-pyran- 2-carboxamide 62 using p-toluenesulfonic acid as a catalyst in an equivalent mixture of DMF and benzene at 100 °C for 4 hours57, S8. Corresponding conversion of 3-cyclohexane carboxamide 63 to bicyclic lactam 64 has never been accomplished54. ... 

Table 8. Bulk polymerization of 8-oxa-6-azabicyclo[3.2.1 ]octan-7-one 61S8 ...

When 269 was treated with SnCU in presence of sodium bicarbonate at — 78 °C, (2/ ,5/ )-5-hydroxy-2-phenyl-3-oxa-l-azabicyclo[3.3.0]octan-8-one 274 was formed (Equation 41) <2006TA53>. 

A comparison of structures of V-methyl-V-nitroso-p-nitrobenzamide, N,N -dimethyl-V-nitrosourea, V-methyl-V-nitrosourea, 2-nitroso-2-azabicyclo[2.2.2]octan-3-one to those of V-methyl-V -nitro-V-nitrosoguanidine and V,V -dimethyl-V"-cyano-V-nitrosoguanidine shows that the N—N and C—NNO bond lengths in the nitroguanidines44 are similar to those found in the nitrosoamides, but that the corresponding bonds in... 

The populations of the rotamers are affected by steric effects. Karabatsos and Taller (77) examined the populations of unsymmetrical nitrosamines and found that in methyl-terr-butylnitrosamine only one isomer was observable. Nelsen and associates (78) similarly found that the populations of conformers of 2-nitroso-2-azabicyclo[2.2.2]octanes (40) are affected by the substituent in the 3-position. 

The alcohol portion in hyoscyamine is tropine in hyoscine it is the epoxide scopine. Tropine is an example of an azabicyclo[3,2,l]octane system with a nitrogen bridge, whereas scopine is a tricylic system with a three-membered epoxide ring fused onto tropine. Note that systematic nomenclature considers an all-carbon ring system with one carbon replaced by nitrogen hence, tropane is an azabicyclooctane (see Section 1.4). 

A new methodology for the construction of novel and uniquely shaped 3-azabicyclo[4.2.0]octan-4-one derivatives 166 by combining the Ugi multi-component reaction with [2 + 2] enone-olefin photochemical transformations was recently reported [132] (Fig. 32). The additional functional groups are in this case an enone (165) and a C=C double bond. Although the overall sequence is capable of creating up to five stereocentres, in most cases only two diastereomers are observed, which are epimeric at the exocyclic stereogenic centre. 

Similarly, azabicyclo[3.2.2]nonanes 426 were produced from bicyclo[2.2.2]octan-2-ones 425 (equation 180). 

One exception is the reaction of acetone oxime with divinyl ketone in the presence of an equimolar amount of zinc(II) bromide (162). Acetone oxime reacts with divinyl ketone on heating in THE at reflux, leading to both conjugate addition and nitrone cycloaddition, producing a 5 1 mixture of regioisomers with 8-oxa-l-azabicyclo[3.2.1]octan-4-one as the major isomer (Scheme 11.42). On the other hand, in the presence of an equimolar amount of zinc(II) bromide, 7-oxa-l-azabicyclo[3.2.1]octan-4-one is the major isomer (97 3) in a total yield of 97%, indicating that the Lewis acid has controlled the regioselectivity of the second step, namely, the cycloaddition. 

Spiro (6R, 7R )-7-acetyl-3-oxa-l-azabicyclo[4.2.0]octan-8-one-2,i -cyclohexane] yield 75%... 

The majority of transformations carried out at ring substituents of bicyclic azetidinones were described in Section 5.12.3.3.2 for azetidinones related to cephalosporins and penicillins. Nucleophilic displacement reactions of 7-halo-l-azabicyclo[4.2.0]octan-8-ones with thallium phthalimide and hydrazine have been reported (76ACS(B)318). 

Conversion of oximes derived from cyclobutyl ketones to amides represents the classic Beckmann rearrangement. One example of this reaction is the formation of optically active 7,7-dimethyl-2-azabicyclo[4.1.1]octan-3-one (1) from 6,6-dimethylbicyclo[3.1.1]heptan-2-one oxime, which is readily derived from /3-pinene.40... 

From the reaction mixture of 3-methyl-2-/er/-butyl-6,7,8,9-tetrahy-dropyrido[l,2-a]pyrimidin-4-one 653 in a 1 2 mixture of acetic acid and acetonitrile under argon at 0°C, after photolysis with a high-pressure mercury lamp, 6-acetoxy-l-azabicyclo[4.2.0]octan-8-one 654, 1-azabicyclo [4.2.0]oct-5-en-8-one 655, and piperidone derivative 656 could be isolated in 72%, 7%, and 1% yields, respectively [88JCS(P1)2653]. 

An ab initio study of the acid hydrolysis of the lactam l-azabicyclo[2.2.2]octan-2-one (described as a highly twisted amide ) and of the model compound 3-methyl-S-valerolactam showed that both proceed via a stepwise mechanism, but A-protonation is preferred to O-protonation by the twisted amide , whereas the reverse is the case for the model compound.92... 

The water-promoted hydrolyses of a bicyclic amide, l-azabicyclo[2.2.2]octan-2-one (87), and a planar analogue, l,4-dimethylpiperidin-2-one (88), were studied using density functional theory in conjunction with a continuum dielectric method to introduce bulk solvent effects. The aim of these studies was to reveal how the twisting of the C-N bond affects the neutral hydrolysis of amides. The results predict important rate accelerations of the neutral hydrolysis of amides when the C-N bond is highly twisted, the corresponding barrier relaxation depending on the specific reaction pathway and transition state involved.85... 

P-unsaturated carbonyl compounds. In a recent example, the products of an Ugi four-component reaction, such as amide 10S, were converted photochemically into uniquely shaped 3-azabicyclo[4.2.0]octan-4-ones, such as cyclobutane 106 (Scheme 6.38) [101]. 

Oxa-3-azabicyclo[3.2.1]octan-2-one (65) derived from methyl furoate was allowed to polymerize in bulk with its N-acetyl derivative as the initiator, and... 

Mullen G, Napier J, Balestra M, DeCory T, Hale G, et al. 2000. (-) -Spiro [ 1 -azabicyclo [2.2.2] octane-3,5 -oxazolidin-2 -one], a conformationally restricted analogue of acetylcholine, is a highly selective full agonist at the alpha-7 nicotinic acetylcholine receptor. J Med Chem 43 4045-4050. 

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