Galal A. Elsayed

Synthetic Utility of Enaminonitrile Moiety in Heterocyclic Synthesis: Synthesis of Some New Thienopyrimidines

The hitherto unknown 3-amino-5-bromo-4, 6-dimethylthieno [2, 3-b] pyridine-2-carbonitrile ( 4 ) was condensed with p-anisaldehyde affording the Schiff base ( 5 ). Acylation of the thienopyridine derivative ( 4 ) using freshly distilled acetic anhydride gave a mixture of mono and diacetyl derivatives ( 6 ) and ( 7 ). Condensation of ( 4 ) with triethylorthoformate yielded the ethoxymethyleneamino derivative ( 8 ), which was treated with hydrazine hydrate to give the hydrazide derivative ( 9 ), which in turn was converted to a triazolopyrimidine derivative ( 10 ) upon treatment with freshly distilled acetic anhydride. Thiation of ( 4 ) with carbon disulfide afforded the pyrimidine dithione derivative ( 11 ), which was alkylated with ethyl iodide to give the di-s-ethylpyrimidine derivative ( 12 ).On the other hand, treatment of ( 4 ) with formamide yielded the aminopyrimidine derivative ( 13 ), whereas its treatment by formic acid produced the thienopyrimidinone derivative (1 4 ). Chlorination of (1 4 ) with a mixture of phosphorus pentachloride and phosphorus oxychloride gave the chloropyrimidine derivative ( 15 ), which in turn afforded the hydrazide derivative ( 9 ) upon treatment with hydrazine hydrate. Hydrazinolysis of ethyl-3-amino-5-bromo-4,6-dimethylthieno[2,3-b]pyridine-2-carboxylate ( 17 ) gave the hydrazino derivative ( 18 ), which in turn was converted to 8-bromo-7,9-dimethyl-3-formylaminopyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one ( 19 ) and 8-bromo-3-diacetylamino-2,7,9-trimethylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one ( 20 ) upon treatment with formic acid and freshly distilled acetic anhydride, respectively.

Dodecanoyl isothiocyanate and N′-(2-cyanoacetyl) dodecanehydrazide as precursors for the synthesis of different heterocyclic compounds with interesting antioxidant and antitumor activity

ABSTRACT Dodecanoyl isothiocyanate 1 was utilized for the construction of thioureido, 2-thioxo-2,3-dihydroquinazolin-4(1H)-one, benzo[d]-1,3-thiazin-4(H)-one and 3-amino quinazolin-4(3H)-one derivatives 2, 3, 4, and 5 respectively. However, N′-(2-cyanoacetyl) dodecanehydrazide 6 was also used as a key starting material for the construction of a variety of new pyrazolone, pyrazole, thiadiazole, pyridazine, chromeno[2,3-c]pyrazole, and dithiolane derivatives 7, 9, 12, 15, 18, and 20, respectively. The newly synthesized compounds were characterized by elemental analyses and spectral data (IR, 1H NMR, and mass spectra). Some of the newly synthesized compounds bearing heterocyclic moieties were tested for antioxidant activity as reflected in their ability to inhibit oxidation in rat brain and kidney homogenates using 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) inhibition. Also, in vitro anticancer activity was examined using the standard (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) (MTT) method against a panel of two human tumor cell lines namely; hepatocellular carcinoma HepG2 and mammary gland breast cancer MCF-7. Compounds 12 and 16b exhibited the highest activities as antioxidant and antitumor agents. Meanwhile, compounds 7 and 20 showed moderate activities and the rest of the tested compounds showed weak activities. GRAPHICAL ABSTRACT

Utility of chloroacetonitrile in construction of some hitherto novel pyrazole and thiazole derivatives

Abstract2-(-Piperidin-1-yl) acetamide (2) was easily prepared by reacting chloroacetonitrile with piperidine. Furthermore, (2) was allowed to react with different aromatic aldehydes to afford novel arylidene derivatives (3a,b). Unexpectedly, 2-oxo-4-hydroxy-thiazole (5) was obtained instead of 2-(piperidin-1-yl-methylene) thiazolidin-4-one (4) when (2) was treated with mercaptoacetic acid under fusion conditions. Subsequent treatment of (5) with aromatic aldehydes and either malononitrile or cyanoacetamide (1:1:1 molar ratios) produced the hitherto unknown pyrano[2,3-d] thiazole derivatives (6a,b) and (7). Novel pyrazole derivatives (8a, b) and (9) were synthesized upon cyclocondensation of (2) with aromatic aldehydes and hydrazine hydrate. Unfortunately, attempts to prepare novel isoxazole derivatives by utilizing hydroxylamine instead of hydrazine hydrate following the previous procedure were failed. Surprisingly, the uncyclized products (10a,b) were obtained rather than 3-hydroxy-4-piperidinyl-isoxazole (11a,b). Upon refluxing thiosemicarbazide with (2) and aromatic aldehydes under the same conditions, pyrazolinone carbothioamides (12), (13) and (14a-c) were obtained.

One-pot synthesis, spectroscopic characterization and DFT study of novel 8-azacoumarin derivatives as eco-friendly insecticidal agents

A series of sixteen 8-azacoumarin derivatives bearing aryl moieties at C-5 and C-7 was designed and synthesized by a concise and facile procedure utilizing grinding and ultrasound approaches. The efficient multi-component protocols proceeded smoothly and in the absence of solvent to furnish the target products in moderate to good yields. All the synthesized molecules were characterized via 1HNMR, 13CNMR, IR, mass spectra, and elemental analyses. The density functional theory (DFT) was then used to discover the structural and electronic characteristics of such compounds. Finally, an insecticidal study against Plutella xylostella and Helicoverpa armigera on the synthesized compounds is reported. The bioassay results indicated that some of the tested compounds showed potency ranging from good to moderate. In particular, analogs 6i and 6l, among the tested compounds, showed even more potency than commercial chlorpyrifos. On the other hand, the rest of the tested compounds showed moderate to weak activities.

Synthesis and Pharmacological Activities of Pyrano[2,3-d]pyrimidine and Pyrano[2,3-d]pyrimidine-5-one Derivatives as New Fused Heterocyclic Systems

Various fused oxazine such as 4-(4-methoxyphenyl)-3,7-dimethyl-1,4-dihydro-5H-pyrazolo [4′,3′:5,6]pyrano[2,3-d][ ]oxazin-5-one 2 has been prepared and utilized as a starting material for novel pyrazolopyranopyrimidinones 3, 5, 6, and 7a–c and pyrazolopyranopyrimidines 4, 9, 10, and 11 which are expected to possess considerable chemical and pharmacological activities. The structures of the new compounds have been elucidated by spectroscopic data and elemental analysis. The antioxidant and anticancer activities of synthesized products have been evaluated.