General Papers ARKIVOC 2009 (vii) 237-246
the literature, the hydrazide compound 6 precipitated after the reaction mixture has reached the RT, thus avoiding the evaporation step and chloroform work up. From the mother liquor the free amino-penicillin amide 5 (6-APABn), presumably formed via 7a and/or 7b intermediate, was isolated by acid-base extractions in 12% yield. 1H and 13C NMR of compound 5 showed no signals that could be attributed to phthaloyl moiety, confirming successful dephthaloylation and formation of new NH2 group, found as a broad singlet at 2.16 ppm.
H
N
O
S
HN N
NH
O Bn
Me-NH-NH2
Me N
CH2Cl2
OH
r.t. -75 °C
7a
H
N
O
O N
S
H2N
S
S
NN
NMe
Me NH2
O
O Bn
+
N NH
ON
N
O Bn
OH
O Bn N
7b
NO
OH OH
36
5
H
N
O
S
HN N NH2-NH2
NH2
O Bn
r.t. CH2Cl2 N -75 °C
OH
8
O O O Scheme 3
When the hydrazinolysis was carried out under the same conditions but using hydrazine instead of methyl hydrazine, no product 5 was isolated. Monitoring the reaction by HPLC/MS corresponding intermediate hydrazino-adduct 8 was found (Scheme 3). We assume that hydrazine and methylhydrazine nitrogens are all basic enough for the first nucleophilic attack on ester-carbonyl group and formation of intermediates 7a, 7b and 8. However, the second intramolecular nucleophilic attack on amido-carbonyl group and the separation of phthalhydrazide in the case of intermediate 8 did not proceed under the same conditions. Based on this, it might be that in the reaction with methylhydrazine only intermediate 7a closes to hydrazide 6 giving the free amino-compound 5 that could contribute to the low yield of compound 5. The other side-reaction, adding further to the low yield of compound 5 is the
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