Lactams amidines, cyclic

A wide variety of /3-lactams are available by these routes because of the range of substituents possible in either the ketene or its equivalent substituted acetic acid derivative. Considerable diversity in imine structure is also possible. In addition to simple Schiff bases, imino esters and thioethers, amidines, cyclic imines and conjugated imines such as cinnamy-lidineaniline have found wide application in the synthesis of functionalized /3-lactams. A-Acylhydrazones can be used, but phenylhydrazones and O-alkyloximes do not give /3-lactams. These /3-lactam forming reactions give both cis and /raMS-azetidin-2-ones some control over stereochemistry can, however, be exercised by choice of reactants and conditions. 

Cyclocondensation of 3-trifluoroacetyl substituted lactams with cyclic 1,3-bisnucleophiles gives pyrimido[l,2-a]benzimidazoles 21 and l,2,4-triazoloI4,3-a]pyridines 22. The use of amidines yields pyrrolopyrimidines <95JCS(P1)2907 94H(37)915>. 

Pyrimido[2,l- ][l,3]thiazinones 363 formed in low yield - instead of the targeted lactams 362 - on photoirradiation of the cyclic amidines 361 and the diazoketone 360 (Scheme 59). Under microwave conditions only 362 formed, which on photoirradiation decomposed <2005JOC334>. 

These results can be readily explained. For instance, the reaction of cyclic amidine 214 with hydroxide ion in water must give first the tetrahedral intermediate 220, which after appropriate proton transfer (+22U can only give the aminoamide 216 with stereoelectronic control. In order to form the lactam 21ji, intermediate 220 must undergo a conformational change to intermediate 222 followed by an appropriate proton transfer (+223). Since lactam 218 is not observed under kinetically controlled conditions, the conformational change 220 222 cannot compete with the breakdown of 220 via 221. Lactam 21 8 is then slowly formed from aminoamide 216 na intermediate 222. 

Diazabicyclo[4.3.0]nonene-based peptidomimetics with a quaternary chiral centre are prepared via intramolecular condensation of A -aminopropyl-y-lactam [27]. Reductive amination of oxazolidinone aldehydes with A -monoprotected propylenediamine give A -phthalimidopropyl lactams however, trials of cyclization to bicyclic amidines after deprotection under dehydration conditions are unsuccessful. To solve this problem, the phthalimides are converted to thiolactams with Lawesson reagent. Deprotection followed by treatment with mercury (11) chloride (HgCl2) yields desired cyclic amidines (Scheme 3.14). 

Titanium tetrachloride Cyclic amidines from lactams... 

Formamidines s. 10, 329 cyclic amidines from lactams, 4-amino-l,5-benzo-diazepines, s. A. Bauer et al., J. Med. Chem. 16, 1011 (1973)... 

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