CHOTosN3NH2R1NHNTosR1NHNTosR1HNR2R3NNTos4-O2NC6H4N3HNR3R2NNNArNR2R3NNArR3R24-O2NC6H4N3NH2RNo products123 (63%) 45H3COOCTosN3R1121,2a 1,2b 1,2c 1,2d 1,2e 1,2f 1,2g 1,2h 1,2iC2H5 CH(CH2)4 C6H5 CH(CH3)COOCH3 CH[CH(CH3)2]COOCH3CH2COOCH3 CH(CH2C6H5)COOCH3 CH(C6H5)COOCH3 CH2CH2SCOCH35 41 33 38 45 39 29 29 3922 19 15 24 32 20 23 19 224,5a 4,5b 4,5cR2 R3CH2CH2OCH2CH2 CH(COOCH3)CH2CH2CH2 CH(COOCH3)CH2SCH2ArYield (%) 5Yield% 24 55 512-I-C6H44-O2NC6H44-O2NC6H4
Scheme 2
The same conditions were chosen for the reaction with 4-nitrophenylazide, but an equimolar amount of phenylacetaldehyde, a suitable secondary amine and 4-nitrophenylazide yielded the stable triazoline 4 which, through prolonged heating, was transformed into the N-aryl-2- benzylamidine derivatives 5 as the main products. No reaction occurred when phenylacetaldehyde was reacted with primary amines and 4-nitrophenylazide and the same behaviour was observed starting from a-amino acid esters. As demonstrated below, this multicomponent reaction proved to be an efficient way to achieve useful intermediates for synthetic transformations. As the structures of the N-tosyl-benzylamidines 1d-i, obtained from linear a-amino acid esters, and of the aryl-benzylamidines 5b-c, obtained from cyclic a-amino acid esters, are quite similar, we proposed to take advantage of the a-amidine methylene group, as well as of the presence of the ester moiety. By carrying out the reaction under basic conditions, an intramolecular condensation providing an heterocyclic ring could be expected between the nucleophilic methylene group4 and the ester function (Scheme 3).
NR2ONHR1NNR1ROOCR2XX
Scheme 3
