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SYNTHESIS, SPECTRAL STUDIES AND ANTI MICROBIAL ACTIVITY OF SOME NOVEL SCHIFF
BASES OF 2-AMINOTHIAZOLO-[5, 4 b]-PYRIDINE
SupervisorDr. M. N.
Noolvi
Co Supervisor
Presented ByAnis Mustafa
M.PHARM.{PHARMA.CHEM. IV SEM}Enroll. N0. 7936776
CHEMISTRY OF THIAZOLOPYRIDINE
Thiazolopyridine is a planar and rigid aromatic system with two condensed heterocycle, which have different π conjugation.
It is a fused system containing a pyridine ring, in which the thiazole ring is fused to pyridine ring. It contain four possible isomers as
[1,3]thiazolo[4,5-b]pyridineN
S
NN
N
S
[1,3]thiazolo[5,4-b]pyridine
1
2
345
67
N
S
N
[1,3]thiazolo[4,5-c]pyridine
N
N
S
[1,3]thiazolo[5,4-c]pyridine
SCHEME OF SYNTHESIS OF 2-AMINOTHIAZOLO-[5, 4 b]-PYRIDINE
N
NH2
Cl+ KCNS + Conc HCl
C2H5OH
66 hours reflux
NH+
NH3+
S
N
N
N
SNH2
2-chloropyridin-3-am ine
[1,3]thiazolo[5,4-b]pyridin-2-am ine
NH 4OH
Reaction Details
Reagent - KCNS and aq. HCl Solvent - ethanol Time - 66 h Other Conditions - Heating Yield - 27 %Melting Point – 240 -242 0CSpectra – I R and 1H NMRRef - H. W. Altland, G. A. Molander, J.
Heterocyclic Chem. 14 (1977) 129-134.
SCHEME OF SYNTHESIS OF
N Cl
N+
O -
O
N
N+
O -
O
SN
N S
NNH2
N S
NNH2
[1,3]thiazolo[5,4-b]pyridin-2-am ine
3-nitropyridin-2-yl thiocyanate2-chloro-3-nitropyridine
+ KCN + DMF
100 0C
5 hours
2 Aminothiazolo(5,4-b)pyridine 3 -oxide
C2H5OH
palladised carbon
hydrogenation3 atm24 hours
a or b
C 2H5OH
CHO
R
N
N
SN
N-benzylidene[1,3]thiazolo[5,4-b]pyridin-2-am ine
R
Reaction Details1. 3-Nitro-2-thiocynatopyridine
Solvent – N,N-dimethylformamide Time - 5 h Other Conditions - Heating 100 0 CYield - 56 %Melting Point – 119 -120 0CMass spectrum – M+ 151 at m/e
2. 2-Aminothiazolo(5,4-b)pyridine 3-oxide
Solvent - ethanol Time - 24 h Other Conditions – Hydrogenation Yield - 68 %Melting Point – 197-198 0CMass spectrum – M+ 167 at m/eAnalysed by nmr
3 a. 2-Aminothiazolo(5,4-b)pyridine
Reagent – Titanium trichlorideSolvent - ethanol Other Conditions – evaporation to dryness Yield - 60 %Melting Point – 250-2520CMass spectrum – M+ 151 at m/eAnalysed by nmr
3 b. 2-Aminothiazolo(5,4-b)pyridine
Reagent – Glacial acetic acidSolvent - ethanol Other Conditions – Hydrogenation at 3 atmTime – 2 daysYield - 62 %Melting Point – 250-2520CMass spectrum – M+ 151 at m/eAnalysed by nmrRef - A. Petric, B. Stanovnik, M. Tisler, B.Vercek,
Vestnik Slovenskega Kemijskega Drustva 25 (1978) 31,34 .
Scheme 3 :-
N
NH2
Cl+ N Cl
NHCSNHCOOEt
N
N
SNH2
C2H5OH
CHO
R
2-chloropyridin-3-am ine
N
N
SN
N-benzylidene[1,3]thiazolo[5,4-b]pyridin-2-am ine
R
[1,3]thiazolo[5,4-b]pyridin-2-am ine
EtOOCNCS
N
N
SNHCOOEt
Ethoxycarbonyl isothiocynate
ethyl [1,3]thiazolo[5,4-b]pyridin-2-ylcarbam ate
CHCl310 min reflux
NaOH 2 days
Reaction Details
Reagent – NaOHSolvent - ethanol Time – 2 daysYield - 37 %Melting Point –246-2510CMass spectrum – M+ 151 at m/eAnalysed by nmrRef - A. Petric, B. Stanovnik, M. Tisler,
B.Vercek, Vestnik Slovenskega Kemijskega Drustva 25 (1978) 31,34 .
Scheme 4 :-
N Cl
NH2
N Cl
NHNH 2
N Cl
NHNHCSNHCOOC 2H5
N S
NNH2
[1,3]thiazolo[5,4-b]pyridin-2-am ine
2-chloropyridin-3-am ine 2-chloro-3-hydrazinylpyridine
+ NaNO 2 + SnCl2
Stirring0 0 C2 hours
extractiondiethyl ether
EtOOCNCS
reflux1 hr
CH 3OH
80 % Hydrazine hydratereflux 2 hr
C2H5OH
CHO
R
N
N
SN
R
N-benzylidene[1,3]thiazolo[5,4-b]pyridin-2-am ine
Reaction Details
Reagent – 80 % hydrazine hydrateSolvent - methanol Time – reflux 2 hrOther condition - Heating Yield - 61 %Melting Point –252-2540CMass spectrum – M+ 151 at m/eAnalysed by nmrRef - B. Koren, B. Stanovnik, M. Tisler,
Monatshefte fur Chemie 119 (1988) 333-339.