Kamal A. Kandeel

Reactions of 5-Aroylmethylene-3-benzyl-4-oxo-2-thioxo-1,3- thiazolidines with Nitrile Oxides.

E,Z-5-Aroylmethylene-3-benzyl-4-oxo-2-thioxo-1,3-thiazolidines (3a-c) react with 4-methoxy and 4-chlorophenylnitrile oxides (4a and b) in pyridine solution to afford one or more of the following compounds: Z-3, Z-2,4-dioxo analogues 5 and 3,6-diaryl- 1,4,2,5-dioxadiazines (6a-b). The interconversion route is discussed and the structures of all of the synthesised compounds are proven by microanalytical and spectral data.

The behaviour of N,N-disubstituted 5-arylmethylidene-2-aminothiazole-4(5H)-ones towards cyclic CH acids and ethyl cyanoacetate

N,N-Disubstituted 5-arylmethylidene-2-aminothiazol-4(5H)-ones reacted with uracil, dimedone and ethyl cyanoacetate to give adducts as a result of addition at the β-terminal of the azomethine moiety and/or addition at the β-carbon of the α,β-unsaturated carbonyl system.

Behaviour of some 2(3H)-furanones bearing a pyrazolyl group as alkylating agents

5-Aryl-3-(1,3-diphenylpyrazol-4-ylmethylene)-2(3H)-furanones (1a–c) were prepared by condensing 1,3-diphenyl-pyrazole-4-carboxaldehyde with 3-aroylpropionic acids in the presence of N,N-dimethyl(chlorosulfinyloxy)meth-animinium chloride as a cyclodehydrating agent. The reactions of these furanones with anhydrous aluminium chloride in benzene, toluene and anisole led to the formation of 4,4-diaryl-1-(1,3-diphenylpyrazol-4-yl)buta-1,3-diene-2-carboxylic acids (6) as mixtures of two geometrical (E,E- and E,Z-) stereoisomers. The unfavoured intramolecular alkylation of 1a–c compared with other furanones is discussed using Hyper Chem Professional (7) AM1 calculations.

The (E)/(Z)-ratio in the reaction of 5-(2-aryl-2-oxoethyl)-2-thioxo-4-oxo-1,3-thiazolidines with bromine

Summary3-Aryl-, 3-benzyl-, and 3H-5-(2-aryl-2-oxoethyl)-2-thioxo-4-oxo-1,3-thiazolidines3a–h react with bromine in acetic acid solution to give mixtures of the respective 5-aroylmethylene (E) and (Z) diastereomeric derivatives5 and6. They contain more than 85% of the (E)-diastereomers along with some pure isomers. The intermediacy of the 5-bromo derivatives4 is proven and a plausible route of the reaction is presented. Structures of compounds3–6 are evidenced by analytical and spectral data.Zusammenfassung3-Aryl-, 3-Benzyl- und 3H-5-(2-Aryl-2-oxoethyl)-2-thioxo-4-oxo-1,3-thiazolidine3a–h reagieren mit Brom in essigsaurer Lösung zu Gemischen der entsprechenden diastereomeren 5-Arylmethylen-Derivate ((E) und (Z))5 und6. Sie enthalten mehr als 85% des (E)-Diastereomeren. Die intermediäre Natur der 5-Brom-Derivate4 wird bewiesen; ein Reaktionsweg wird vorgeschlagen. Die Strukturen der Verbindungen3–6 werden durch analytische und spektroskopische Daten abgesichert.

Reactions of N,N-Disubstituted 5-Arylmethylidene-2-amino-thiazol-4(5H)-ones with CH Acids

Summary. N,N-Disubstituted 5-arylmethylidene-2-aminothiazol-4(5H)-ones reacted with diethyl malonate, ethyl benzoylacetate, acetylacetone, or cyclopentadiene in refluxing toluene and in presence of powdered sodium to give the respective 5-arylmethylidene-2′-amino-2,5′-bithiazolylidene-4,4′-dione derivatives in moderate yields. 5-Benzylidene-2-morpholin-4-yl-2-thiazol-4(5H)-one reacted with malononitrile in toluene and in presence of powdered sodium under mild conditions to afford the 1:1 adduct, benzylmalononitrile, and 2-morpholin-4-yl-2-thiazol-4(5H)-one. However, similar treatment of 5-(4-methoxyphenylmethylidene)-2-morpholin-4-yl-2-thiazol-4(5H)-one with malononitrile yielded the 2,5′-bithiazolylidene-4,4′-dione derivative together with 4-methoxyphenylmethylidene malononitrile. Treatment of 5-benzylidene- and 5-(4-methoxyphenylmethylidene)-2-morpholin-4-yl-2-thiazol-4(5H)-ones with 3-phenyl-4-oxo-2-thioxo-1,3-thiazolidine in refluxing toluene and in presence of powdered sodium produced 5-arylmethylidene-3-phenyl-4-oxo-2-thioxo-1,3-thiazolidines in good yields. The structures of all products were deduced from microanalytical and spectroscopic data, mechanistic details are discussed.

REACTIONS OF 5-SUBSTITUTED-2-THIOXO-4-OXO-1,3-THIAZOLIDINES WITH 4-METHOXYPHENYLAZIDE

Abstract 4-Methoxyphenylazide cycloadds to the thiono function and undergoes nucleophilic attack at other electrophilic centers of 5-benzoylmethyl-(1a) and E,Z-5-(4-bromobenzoylmethylene)-(E,Z-2b) -2-thi-oxx-4-oxo-1,3-thiazolidines in non site selective reactions to afford variety of products. With la, the attack at the thiono as well as the hetero-ring carbonyl functions leads to the 5-benzoylmethylene-2-(4-methoxyphenylimino)-derivative (3) and the ring fission product 2–4. Similar treatment of E,Z-Zb gives a mixture of the respective E,Z-2-(4-methoxyphenylimino)-derivative (E,Z-5) containing 80% of the Z-configurated isomer (Z-5) and the ring enlarged thiazinonethione derivative (6), due to the attack at the thiono and exocyclic double bond functions, respectively. Rationalizations for the above mentioned conversions are given. Structures of all products are evidenced by microanalytical and spectral data.

Conversion of 5-Aryl-3-phenylthio-2(3H)-furanones into Some Nitrogen- and Sulphur-Containing Heterocycles

3-Phenylthio-5-aryl-2(3H)-furanones 4 were prepared from 2-phenylthio- 3-aroylpropionic acids 3 by a ring closure using acetic anhydride. Benzylamine reacted with 4 to give the benzylamide derivatives 5, which were cyclized to the corresponding 2(3H)-pyrrolones 6. The isothiazolone derivatives 7 were obtained from the benzylamides 5 by the action of SOCl2. A ring opening of furanone 4 with hydrazine hydrate gave the acid hydrazides 8. The latter hydrazides were utilized as starting materials for the synthesis of pyridazinone derivatives 9 and 11, 1,3,4-oxadiazoles 13, and triazolone derivatives 14.

Synthesis and antitumor activity evaluation of some novel pyrazolotriazine derivatives

ABSTRACT 6-Aminopyrazolo[1,2-a][1,2,4]triazine-4,8-dione derivative 3 was obtained upon the reaction of the acid hydrazide derivative 2a with ethyl cyanoacetate. The reactions of 3 with several electrophiles such as aldehydes, isatin, acetic anhydride, phenyl isocyanate, benzoyl isothiocyanate, and p-toluenesulfonyl chloride were studied. The structures of the newly synthesized compounds were established on the basis of IR, 1H NMR, mass spectra, and elemental analyses. The antitumor activities of some selective compounds were examined against two cell lines as liver carcinoma cell line (HEPG-2) and human breast cancer cell line (MCF7). GRAPHICAL ABSTRACT