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.

IR Spectra

NMR Spectra

NMR Spectra

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.

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