الفهرس 
Recent Developments in Chemistry of 1,3,4- ThiadiazolesOnly 14 pages are availabe for public view
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Abstract
The current work illustrates the versatile role of 5- cyanomethyl thiadiazole and 2-aminothiadiazole derivatives in the synthesis of different heterocyclic systems from simple readily obtainable materials.
The work can be divided into three main parts:-
i- Synthesis of 5-cyanomethylthiadiazol and its reactions.
ii- Synthetic utility and chemical behaviour of 2-aminothiadiazole derivative.
iii- Study of insecticidal activity of the synthesized compounds.
First part: Synthesis of 5-cyanomethyl thiadiazole and its reactions:-
2-Chloro-N-(5-(cyanomethyl)-1,3,4-thiadiazol-2-yl)benzamide (5) has been synthesized via reaction of 2-chlorobenzoyl chloride 1 with ammonium thiocyanate in dry acetonitrile to afford the 2-chlorobenzoyl isothiocyanate 2, to which cyanoacetohydrazide 3 was added in situ with stirring, then refluxing the produced 2-chloro-N-(2-(2-cyanoacetyl)hydrazine-1-carbonothioyl)benzamide (4) in glacial acetic acid. Heterocyclization of 5 with thioglycolic acid in dry pyridine afforded the thiazolidinone derivative 6, which reacted with p-nitrobenzaldehyde in presence of anhydrous sodium acetate as a catalyst in glacial acetic acid to afford the product 7 [cf. scheme I].
Scheme I
Also compound 5 reacted with heterocyclic and aromatic aldehydes namely, 1,3-diphenyl-1H-pyrazole-4-carbaldehyde, 4-(dimethylamino)benzaldehyde and 4-methoxybenzaldehyde in the presence of drops of piperidine as a basic catalyst to yield the expected condensation products 8, 10 and 11, respectively.
Hydrazinolysis of compound 8 with hydrazine monohydrate in boiling dioxane afforded 3,4’-bipyrazole derivative 9. The compound containing indolinone moiety 12 and 2-carbohydrazonoyl cyanide 13 were synthesized from the condensation of isatin and p-anisidine diazonium chloride with compound 5 [cf. scheme II].
Scheme II
At room temperature, reaction of compound 5 with phenyl isothiocyanate and carbon disulphide in dimethyl formamide (DMF) containing KOH gave the intermediate A and intermediate B, respectively. Firstly, in situ acidification of the intermediate A with dil HCl awarded 14. Secondly treatment of the intermediate A with ethyl chloroacetate afforded the uncyclized product 15. Similarly, the uncyclized product 17 was obtained instead of the 1,3-dithiolan-4-one moiety 18 when the intermediate B was treated with ethyl chloroacetate [cf. scheme III].
Scheme III
Refluxing compound 5 with salicylaldehyde and benzoin in the presence of a base in ethanolic solution gave iminochromene derivative 19 and furan moiety 20, respectively.
Reaction of compound 5 with phenyl isothiocyanate, acetone and/ or ethyl cyanoacetate in the presence of elemental sulfur under basic condition afforded 2-thioxo-2,3-dihydrothiazole derivative 21, thiophen-2(5H)-imine moiety 22 and / or the corresponding amide derivative 24 [cf. scheme IV].
Scheme IV
Second part: Synthetic utility and chemical behaviour of 2-aminothiadiazole derivative:-
Reaction of m-chlorobenzoic acid with thiosemicarbazide in the ratio (1:1) and ratio (1:2) in the presence of POCl3 afforded benzamide derivative 25 and 5-(3-chlorophenyl)-1,3,4-thiadiazol-2-amine 26, respectively. Further prove for the chemical structure of compound 25 was practically implemented by synthesis of authentic sample through reaction of compound 26 with m-chlorobenzoyl chloride in the presence of pyridine as a basic catalyst [cf. scheme V].
Scheme V
Fusion of compound 26 with freshly distilled acetic anhydride, maleic anhydride and / or phthalic anhydride afforded the monoacetyl 27, maleimide 28 and / or N-phthalimido 29 derivatives, respectively.
Treatment of 2-aminothiadiazole derivative 26 with cinnamoyl chloride, p-toluene sulphonyl chloride and phenyl isothiocyanate furnished N-cinnamoyl derivative 30, p-toluene sulfonamide 31 and phenyl thiourea 32 derivatives, respectively. Condensed product 33 and Schiff base derivatives 34-36 have been obtained via reaction of compound 26 with isatin and variant arylaldehydes [cf. scheme VI].
Scheme VI
Among our endeavors in this thesis, reaction of 2-aminothiadiazole derivative 26 with doubly electrophilic reagents for example, diethyl malonate, ethyl acetoacetate, ethyl benzoyl acetate, acetyl acetone, malononitrile, arylidene malononitrile, to construct various fused-thiadiazole derivatives 37-42 [cf. scheme VII].
Scheme VII
Third part: Study of insecticidal activity of synthesized compounds
Because of the economic importance of the cotton plant crop for humanity and to achieve the main target of the present work, the insecticidal activity of the synthesized heterocyclic systems against cotton leaf worm (spodoptera littoralis) was screened. Generally, the insecticidal potency of the thiadiazoles results from its interference with the RNA in the processes of protein synthesis is affected by the substituent position on thiadiazole ring, as the electron withdrawing of the substituents group, the bioactivity of the synthesized product also increases. Finally, the bioactivity increases as the number of electron deficient groups increase and vice versa.