Mohamed Abass

CHEMISTRY OF SUBSTITUTED QUINOLINONES. III. SYNTHESIS AND REACTIONS OF SOME NOVEL 3-PYRAZOLYL-2-QUINOLINONES

The preparation of 4-hydroxy-1-methyl-3-(5-oxo-4,5-dihydro-1H-3-pyrazolyl)-1,2-dihydro-2-quinolinone (3) and its hydrazono-, aminomethylidene- and arylidene derivatives has been achieved. The synthesis of fused heterocyclic polynuclear systems containing quinolinone moiety is also described.

Chemistry of Substituted Quinolinones. Part VI. † Synthesis and Nucleophilic Reactions of 4-Chloro-8-methylquinolin-2(1H)-one and its Thione Analogue

Mostafa M. Ismail, Mohamed Abass* and Mohamed M. HassanDepartment of Chemistry, Faculty of Education, Ain Shams University, Roxy, 11711 Cairo, Egypt.Tel: + 202 7104060, Fax: + 202 2581243. * Author to whom correspondence should be addressed; E-mail: mohamedabass@hotmail.com† For part V see reference [1].Received: 12 October 2000; in revised form: 2 November 2000 / Accepted: 9 November 2000 /Published:18 December 2000Abstract: The synthesis of 4-chloro-8-methylquinolin-2(1H)-one and its thione analogue is described. Some nucleophilic substitution reactions of the 4-chloro group were carried out to get new 4-substituted 2-quinolinones and quinolinethiones, such as 4-sulfanyl, hydrazino, azido and amino derivatives, which are of important synthetic use. The structure of the new compounds was established by their elemental analysis, IR and

Chemistry of Substituted Quinolinones. Part 8. Synthesis and Cyclization Reactions of Ethyl 5-Amino-1-(1-methyl-2-oxoquinolin-4-YL)-3-methylsulfanylpyrazole-4-carboxylate

The synthesis of the titled amino-ester 3 is described and its hydrolysis and chloroacetylation led to the acid 5 and acetamide 7 , which were cyclized to the pyrazolopyridones 6 and 8 , respectively. Condensation of 3 with 2,5-dimethoxytetrahydrofuran afforded the pyrrolylpyrazole 9 , which underwent cyclization by action of PPA to give pyrazolopyrrolizine 10 . Treating 3 with thiophosgene gave the pyrazolyl isothiocyanate 11 , which added aniline to yield the thiourea derivative 12 , and cyclized to give pyrazolopyrimidinethiones 13-15 . Condensation of 3 with formamide furnished pyrazolopyrimidine 16 , while with triethyl orthoformate produced the ethoxymethyleneaminopyrazole 18 , which condensed with hydrazine to give the aminopyrazoloprimidine 19 . Reaction of 3 with Lawessons reagent resulted in the pyrazolothiazaphosphinine 21 . Also the cyclization reaction of the compound 3 with malononitrile and its mixtures with carbon disulfide, phenyl isothiocyanate, or benzaldehyde led to the formation of a variety of polyfunctional substituted pyrazolopyrimidines 23 and 26 , pyrazolothiazine 24 and pyrazolopyridine 28 .

Substituted quinolinones. 18. 3-Acetyl-4-methylthioquinolin-2(1H)-one as useful synthon intermediate for synthesis of some new quinolinones

Abstract3-Acetyl-4-methylthioquinolin-2(1H)-one (3) has been prepared and its reactivity towards treatment with different reagents, dilute sulfuric acid, aqueous sodium hydroxide, and hydrogen peroxide, is described. The reactions of compound 3 with benzylamine, benzaldehyde, DMF-DMA, Vilsmeier-Haack reagent, 2-chloro-3-formyl-pyridopyrimidone and malononitrile have been carried out under convenient conditions. Compound 3 underwent heterocyclization reactions with some binucleophiles, hydrazine, hydroxylamine, urea, thiourea, semicarbazide, and thiosemicarbazide, furnishing some known five, six, and seven heterocyclic annellated quinolines. All the new compounds have been characterized using different spectral and analytical tools.

Substituted pyridopyrimidinones. Part 5. Behavior of 2-hydroxy-4-oxo-4H-pyrido[1,2-α]pyrimidine-3-carbaldehyde in nucleophilic condensation reactions

Reactivity of 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carbaldehyde (I) towards N- and C-nucleophiles was described. A series of new enaminones II–III, Schiff’s base IV, and hydrazinomethylenediketones V–VIII and X were prepared in good yields. Cyclization of compounds X was achieved by an action of acetic acid to give pyrazolo[3,4-d]pyrido[1,2-a]pyrimidines XI. Base catalyzed Knoevenagel condensation of aldehyde I with some active methyl and methylene compounds led to a series of chalcone-like derivatives XII, XV, XVII, XX, XXIII, XXV, XXVII, XXIX, XXXI, XXXII, and XXXV, in fair yields. Cyclization of enones XII, XV, and XX with hydrazine gave novel heterocyclyl substituted pyrazoles XIII, XVII, and XXI, respectively. Pyrano[2,3-d]pyrido[1,2-a]pyrimidine-2,5-diones XXXIII, XXXIV, and XXXVI derivatives were obtained via cyclization of their respective enone derivatives.

Substituted Quinolinones, Part 11: Efficient Synthesis of Different 3‐(4‐Arylidene and Hetarylidene‐5‐oxopyrazolin‐3‐yl) quinolin‐2‐ones

Abstract Several 3‐(4‐arylidene and hetarylidene‐5‐oxopyrazolin‐3‐yl)quinolin‐2‐ones 6–26 were synthesized in an efficient methodology utilizing both pyrazolinylquinolinone 2 and its chromenylmethylene derivative 10. Compound 2 was derivatized by Knoevenagel condensation with different carbonyl compounds. Nucleophilic ring opening–ring closure (RORC) of the compound 10 furnished the desired 4‐methylenepyarzolinone bearing novel five‐, six‐, and seven‐membered heterocycles, in good yields.

Substituted Quinolinones, Part 12: Heterocyclization Reactions of 3‐(3‐Chromonyl)acryloylquinolinone with Some Bifunctional Nucleophiles

Abstract 4‐Hydroxy‐1‐methyl‐3‐[E‐3‐(4‐oxo‐4H‐chromen‐3‐yl)acryloyl]quinolin‐2(1H)‐one (3) was smoothly obtained via a one‐pot aldol dehydration reaction of 3‐acetyl‐4‐hydroxyquinolin‐2(1H)‐one with 3‐formylchromone and was utilized to prepare miscellaneous triheterocyclic systems containing the quinolinone moiety. Both the α,β‐unsaturated ketone side chain and the γ‐pyrone ring in compound 3 were subjected to nucleophilic cyclization with certain 1,2‐ and 1,3‐bifunctional N,N‐, N,O‐, N,C‐, and O,C‐nucleophiles under different reaction conditions. Many pyrazolinyl‐, isoxazolinyl‐, pyrimidinyl‐, and pyridinylquinolinones bearing other six‐ or five‐membered heterocyclic systems have been conveniently synthesized using more than one synthetic route. Dedicated to the memory of the late Professor Sayed Ibrahim El‐Nagdi.

Substituted Quinolinones, Part 10: Synthesis of Angular Tetracyclic Thieno and Thiopyrano[3,2- c ]benzo[ h ]quinolinones Under PTC Conditions as Novel Enzymatic Enhancers

4-Chlorobenzo[h]quinolin-2(1H)-one (4) and its 4-sulfanyl derivative 6 were smoothly obtained via chlorination, hydrolysis, and sulfurization starting with 4-hydroxybenzo-[h]quinolin-2(1H)-one (1). Heterocyclization reaction of compound 6 with chloroacetaldehyde diethylacetal, phenacylbromide, chloroacetonitrile, ethyl chloroacetate, and bromomalononitrile under phase transfer catalysis (PTC) conditions was described affording benzo[h]thieno[3,2-c]quinolinones 7–9 , 11, 12, and 14. The PTC-nucleophilic substitution of compound 4 with malononitrile gave quinolinylmalononitrile 15, which subsequently cyclized with sulfur/triethylamine (TEA) to afford benzo[h]thieno[2,3-c]quinolinone 16. The PTC reaction of compound 6 with CS 2 and malononitrile gave benzo[h]thiopyrano[3,2-c]quinolinone 18. Similarly, cyclization of compound 4 with thiosalicylic acid furnished benzo[h]thiochromeno[3,2-c]quinolinedione 20. Thermal condensation of compound 6 with ethyl 2-cyano-3-ethoxyacrylate or ethyl 2-cyano-3,3-di(methylsulfanyl)acrylate afforded benzo[h]thiopyrano[3,2-c]quinolinones 22 and 24, respectively. The effect of new 14 products on α-amylase activity was examined. Thienoquinolinones 9, 11, 14, and 16 were the most potent enhancers in which these compounds multiplicate the activity of the enzyme to produce α-D-glucose up to eightfold.

Substituted Quinolinones, Part 14: Synthesis of Novel Dispiro(heterocycle-N,2′-[1,3]dithietane-4′,3″-quinolinedione) Derivatives Under PTC Conditions

Abstract The four-membered spiro-heterocycles ethyl cyano(1-methyl-2,4-dioxospiro{1,3-quinoline-3,4′-[1,3]dithietane}-4′-ylidene)-acetate 2a, -malononitrile 2b, -acetylacetone 2c, and thiazetidine isomer 3 were prepared under phase transfer catalysis (PTC) conditions. The thermal treatment of dithietanes 2a–c led to the bis-quinolinyl sulfide 4. Some interesting nucleophilic additions followed by cyclization reactions were carried out with the dithietane 2a to give the corresponding novel dispiro derivatives 5–8, 10–13, and 15. Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. GRAPHICAL ABSTRACT

Chemistry of Substituted Quinolinones IV. Regioselective Nucleophilic Substitution of 1,3-Dichlorobenzo[f]quinoline

Abstract 1,3-Dichlorobenzo[f]quinoline 2 was obtained from 1-hydroxybenzo[f]quinolin-3-one 1. Nucleophilic substitution, hydrolysis, hydrazinolysis and azidation reactions of compound 2 have been studied and found regioselective. Also, 1-aminobenzo[f]quinolinone 11 was obtained and used to prepare the benzoquinolinylthiourea derivative 12, naphthonaphthyridinedione 13, benzoquinolinylhydrazonoquinoline 15 and benzo[f]-quinolinyl enamine 17.