Chemistry of heteroanalogs of isoflavones

It is shown that treatment of 3-hetarylchromones with alkalis and hydrazine hydrate leads to opening of the pyrone ring and subsequent conversion of the intermediate to -hetaryl-2-hydroxyacetophenones and 2-hydroxyphenylpyrazole derivatives.See [1] for communication IV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1474–1476, November, 1976.     

Synthesis of 2-hydrazino- and 2-amino-1,3,4-thiadiazines containing polyhydric phenol residues in the 5 position

2-Hydrazino-1,3,4-thiadiazines containing polyhydric phenol residues in the 5 position were obtained by reaction of 3,4-dihydroxy-, 2,5-dihydroxy-, and 2,3,4-trihydroxyphenacyl -halides with thiocarbohydrazide. 2-Amino-1,3,4-thiadiazines were obtained by reaction of 3,4-dihydroxy-and 2,5-dihydroxyphenacyl -halides with thiosemicarbazide in acidic and alcoholic media. In contrast to the dihydroxy derivatives, 2,3,4-trihydroxyphenacyl halide forms a 2-amino derivative only in strongly acidic media, whereas the isomeric thiazole compound with a hydrazine group in the 2 position of the thiazole ring is formed in alcoholic media.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1051–1055, August, 1976.     

Synthesis and antimicrobial activity of some new coumarin and dicoumarol derivatives

PTC reaction of coumarin derivative 1 with alkyl halides afforded C₄ oxygen alkylation products 2a-d in appreciative yield, whereas with phenyl isothiocyanate gives the C₃ addition product 4 ; also, one-pot three-component PTC reaction was investigated. Treatment of coumarin 1 with aromatic aldehydes in different molar ratios gives 3-arylidene derivatives 7a,b and the dicoumarol derivatives 8a,b . Pyrano chromene 9 and pyrano pyridine 10 were obtained by reaction of arylidene 7a with ethyl acetoacetate through Michael cycloaddition reaction. The stability of pyrone ring in 3-arylidene 7 and dicoumarol 8 towards different nucleophilic reagents under reflux and/or fusion conditions has been studied by the action of hydrazine hydrate, ammonium acetate, methyl amine, and p-toluidine afforded compounds 11 and 13a-c . The antimicrobial activity of some synthesized compounds has been investigated.     

A study on chemical behaviors of some 4‐pyrones synthesized by one‐step reactions towards various amines

Cycloaddition of acetylbenzoyl ketene generated in situ as an intermediate during one‐step reaction between excess benzoylacetone and oxalylchloride to C=C double bond of cyclic enol form of benzoylacetone gave 3‐acetyl‐5‐benzoyl‐6‐methyl‐2‐phenyl‐4(4H)‐pyrone 1a . Condensation reactions of 1a together with 3,5‐dibenzoyl‐2,6‐diphenyl‐4(4H)‐pyrone 1b and 3‐benzoyl‐5‐ethoxycarbonyl‐2,6‐diphenyl‐4(4H)‐pyrone 1c with two‐fold excess primary amines provided a series of 3‐benzoyl‐1‐alkyl‐5‐(1‐alkylimino‐ethyl)‐6‐phenyl‐2‐methyl‐4(1H)‐pyridinone 2 , 3,5‐dibenzoyl‐1‐alkyl‐2,6‐diphenyl‐4(1H)‐pyridinone 3a‐c and 3‐benzoyl‐1‐alkyl‐5‐ethoxycarbonyl‐2,6‐diphenyl‐4(1H)‐pyridinone 3d,e derivatives, respectively. In addition, while prolonged reaction of n‐pentylamine with unsymmetrical pyrone derivative 1a gives a symmetrical pyridinone derivative namely 3,5‐dibenzoyl‐2,6‐dimethyl‐1‐pentyl‐4(1H)‐pyridinone 5 , much prolonged action n‐pentylamine and then aqueous n‐pentylamine on 1b resulted in degradation of the 4‐pyrone ring to give dibenzoylmethane.     

Reactions of o-bromoacetylacylphenones with several primary amines

o-Monobromoacetylacylphenones, 3a and 3b reacted with hydroxylamine or hydrazine hydrate to produce heterocycles, 2,3-benzoxazine or phthalazine derivatives. The reaction of bromoacetyl group of 3a and 3b with several thioamides afforded thiazole derivatives in high yields. Whereas o-dibromoacetyl-benzophenoe 2a reacted with aniline or cyclohexylamine to produce non-heterocycles, 2-substituted-iminophenylindanones and the mechanism for the formation of these non-heterocycles is proposed.     

Ring transformation of 6-methyl-3,4-dihydro-2H-1,3-oxazine-2,4-diones

Ring transformation of 6-methyl-3,4-dihydro-2H-1,3-oxazine-2,4-dione (Ia) and its N-sub-stituted derivatives, such as 3-methyl (Ib), 3-ethyl (Ic), and 3-benzyl (Id) derivatives is described. Reaction of Ia with hydrazine hydrate gave 1-amino-6-methyluracil (II), while Id reacted with hydrazine hydrate to give 3-hydroxy-5-methylpyrazole (III). Reaction of Ia,b,d with ethyl acetoacetate in ethanol in the presence of sodium ethoxide afforded ethyl 3-acetyl-6-hydroxy-4-methyl-2(1H) pyridone-5-carboxylate derivatives (IVa,b,d). On the other hand, reaction of Ib,c,d with ethyl acetoacetate in tetrahydrofuran in the presence of sodium hydride did not give IV, but gave 3-acetyl-1-alkyl-5-(N-alkylcarbamoyl)-6-hydroxy4-methyl-2(1H) pyridone (VIb,c,d). Mechanisms for the formation of compounds IV and VI are discussed.     

Unsaturated lactones

New, biologically active pyrazole derivatives containing an unsaturated -lactone ring were obtained by condensation of 2-(1-etboxycarbonyl-1,3-diketopropyl)-2-buten-4-olides with phenylhydrazine and hydrazine hydrate. A number of transformations of the resulting pyrazole-3-carboxylic acid esters were realized.See [1] for communication XXXIV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1611–1614, December, 1978.     

Synthesis and some reactions of 4‐(ethoxycarbonyl)‐1,5‐diphenyl‐1H‐pyrazole‐3‐carboxylic acid

1,5‐Diphenyl‐1H‐pyrazole‐3,4‐dicarboxylic acid‐4‐ethyl ester 2 , obtained from the 4‐ethoxycarbonyl‐5‐phenyl‐2,3‐furandione 1 and N‐benzylidene‐N′‐phenyl hydrazine, was converted via reactions of its acid chloride 3 with various alcohols or N‐nucleophiles into the corresponding ester 5 or amide derivatives 6 , respectively. In addition, 2 was decarboxylated to give ethyl 1,5‐diphenylpyrazole‐4‐carboxylate 4 . Nitrile 7 derivative of 2 was also obtained by dehydration of 6a in a mixture of SOCl₂ and DMF. While cyclocondensation reaction of 2 with hydrazine hydrate leads to the formation of pyrazolo[3,4‐d]pyridazine‐4,7‐dione 8 , the reaction of 3 with anhydrous hydrazine provided a new bis pyrazole derivative 9 .     

Transformation of 6‐methylthiopyrimidines. Preparation of new pyrimidine derivatives and fused azolopyrimidines

2,4‐Diamino‐6‐methylthiopyrimidines 1 reacted with sodium methoxyde and benzylamine to give the corresponding 6‐methoxypyrimidine and 6‐benzylaminopyrimidine derivatives 2 and 4 respectively. The reaction of 1 with hydrazine hydrate, in ethanol, gave 6‐hydrazino derivatives 6. However, by treating pyrimidines 1 in boiling hydrazine hydrate 3,6‐diamino‐4‐hydrazino‐1H‐pyrazolo[3,4‐d]pyrimidine 5 was obtained. The 6‐hydrazinopyrimidines 6 could be converted into the pyrazolo[3,4‐d], triazolo[4,3‐c] and tetrazolo‐[1,5‐c]pyrimidines 7, 8 and 9 by the action of heating, trimethyl orthoformate and nitrous acid, respectively.     

Synthesis of 1‐substituted 5‐aryl‐3‐styryl‐2‐pyrazolines and 3‐aryl‐5‐styryl‐2‐pyrazolines by the reaction of dibenzylideneacetones and E,E‐cinnamylideneacetophenones with hydrazines

The reaction of dibenzylideneacetones or E,E‐cinnamylidene‐ acetophenones and hydrazine hydrate provided 1‐propionyl derivatives of 5‐aryl‐3‐styryl‐2‐pyrazolines and 3‐aryl‐5‐styryl‐2‐pyrazolines. These unsaturated ketones afforded 1‐(2‐carboxyphenyl) or 1‐(4‐carboxyphenyl) 5‐aryl‐3‐styryl‐2‐pyrazolines and 1‐(4‐carboxyphenyl) derivatives of 3‐aryl‐5‐styryl‐2‐pyrazolines on treatment with (2‐carboxyphenyl)‐hydrazine or (4‐carboxyphenyl)hydrazine in hot acetic acid. Structures of all new 2‐pyrazolines have been elucidated by microanalyses and a combined utilization of various spectroscopic methods.     

Functionalization and cyclization reactions of 4-benzoyl-1,5-diphenyl- 1H-pyrazole-3-carboxylic acid

The 1H-pyrazole-3-carboxylic acid 2 or its remarkably stable acid chloride 3 can easily be converted into the corresponding ester or amide derivatives 4 or 5, respectively, from reaction with alcohols or N-nucleophiles. Pyrazolo[3,4-d]pyridazines 6a,b are obtained from cyclocondensation reactions of the pyrazoles 2 and 3, respectively, with phenylhydrazine or hydrazine hydrate, while 6c is formed in an one-pot procedure from the furan-2,3-dione 1 and hydrazine hydrate.     

Synthesis and Reactivity of 3‐oxoprop‐1‐en‐1‐olate Derivative as a Building Block for the Synthesis of Azole and Azine Derivatives

Several new heterocyclic compounds such as 7‐substituted pyrazolo[1,5‐a ]pyrimidine ( 5a–e ) derivatives have been synthesized by the reactions of the versatile unreported sodium 3‐(4‐methyl‐2‐(4‐methylphenylsulfonamido)thiazol‐5‐yl)‐3‐oxoprop‐1‐en‐1‐olate (2) with amino heterocyclic ( 3a–e ) derivatives. Reaction of (2) with hydrazonyl halide ( 7a–d ) and hydroximoyl chloride ( 11a,b ) derivatives followed by reaction with hydrazine hydrate afforded pyrazolo[3,4‐d ]pyridazine and isoxazolo[3,4‐d ]pyridazine derivatives, respectively incorporating a thiazole moiety have been described. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis.     

Synthesis of 4-hydroxy-5-methyl-2-[2-(4-oxo-4<Emphasis Type="Italic">H</Emphasis>-chromen-3-yl)ethenyl]-6<Emphasis Type="Italic">H</Emphasis>-1,3-oxazin-6-ones and their reaction with hydrazine

4-Hydroxy-6H-1,3-oxazin-6-ones containing a 3-vinylchromone fragment in the 2-position were synthesized. The direction of their reactions with hydrazine hydrate was found to depend on the solvent nature. The reaction in protic solvents (methanol, acetic acid) resulted in recyclization of both oxazine ring to 1,2,4-triazole and pyranone ring to pyrazole. Aprotic acetonitrile favored attack of hydrazine exclusively on the oxazine ring, while the 3-vinylchromone fragment remained intact.     

General synthesis of: 5-substituted-3-acyl-4-carbethoxypyrazoles 3,6-subslituted-5-carbethoxy-4(h)pyridazinones and 3,7-substitutedpyrazoio[3,4-d] pyridazine-4(5h)ones via reactions between 2-hydroxy,methoxy, and acetoxy-3(2h)furanones and hydrazine

Synthesis of substituted 3-acyl-4-carbethoxypyrazoles, 5-earbethoxy-4(1H)pyridazinones and pyrazolo[3,4-d]pyridazine-4(5H)ones is described. They involve the reaction of the 2,5-substituted-4-earbelhoxy-2-hydroxy, methoxy and acetoxy-3(2H)furanones with hydrazine hydrate. The reaction was found to be dependent on the hydroxy, methoxy or acetoxy substituents of these furanones and proceeds with ring opening followed by cy clisation. Pyrazoles were formed with hydroxy or methoxy substituents while pyridazinones are afforded with acetoxy group. The pyrazoles so formed were readily converted to pyrazolo[3,4-d] pyridazinones by condensation with excess hydrazine.     

Synthesis and Antibacterial Evaluation of Some New Thiazole‐Based Polyheterocyclic Ring Systems

2‐Cyanoacetamido‐thiazole ( 1 ) was employed as a key for the construction of 6‐cyano‐7‐oxo‐7H‐thiazolo[3,2‐a]pyrimidine ( 4 ) which underwent reaction with hydrazine, malononitrile, ethyl cyanoacetate, and/or various 1,3‐bi‐nuclophilic reagents furnished the corresponding tri‐heterocyclic and tetra‐heterocyclic ring systems 5 – 12 . In addition, the reactions of 1 with various types of arylidene‐malononitriles and/or ethyl 3‐aryl‐2‐cyanoacrylates yielded the corresponding 1‐thiazolyl‐pyridine derivatives 16 and 20 , respectively. Furthermore, treatment of the precursor 1 with carbon disulfide and methyl iodide afforded the ketene dithioacetal derivative 21 which cyclized upon heating with hydrazine and/or 2‐aminobenzimidazole into the corresponding derivatives of N‐(thiazol‐2‐yl)‐1H‐pyrazole‐4‐carboxamide 22 and N‐(thiazol‐2‐yl)benzimidazo[1,2‐a]‐pyrimidine‐3‐carboxamide 23 . The antibacterial properties of these thiazole‐based heterocycles were examined against panel of two bacterial strains.     

Synthesis,reactions, and antimicrobial activity of some novel pyrazolo[3,4-d]pyrimidine,pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine,and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c]pyrimidine derivatives

Treatment of N-phenyl-substituted benzenecarbo-hydrazonoyl chlorides 1a - d with malononitrile in sodium ethoxide solution gave 5-amino-4-cyanopyrazole derivatives 2 - 5 . Compounds 2 - 5 were converted to formidate derivatives 6 - 9 upon treatment with TEOF in acetic anhydride. The reaction of the latter products 6 - 9 with hydrazine hydrate gave imino-amino derivatives 10 - 13 , which was converted to hydrazino derivatives 14 - 17 by refluxing with hydrazine hydrate. Hydrazino as well as imino-amino derivatives undergo condensation, cyclization, and cycloaddition reactions to give pyrazolo[3,4-d]pyrimidine 18 - 21 , pyrazolo[4,3-e][1,2,4]triazolo-[3,4-c]pyrimidine 22 - 27 , and pyrazolo[3′,4′:4,5]pyrimido[1,6-b][1,2,4]triazine 42 - 44 derivatives. Antimicrobial studies are performed using two Gram-positive bacteria and two Gram-negative bacteria. Data indicated that compounds 5 , 28D , 29B , and 31D are exploring elevated antibacterial effects against all strains tested. Compound 28D is the most promising antibacterial agent against the delicate bacterial strain Bacillus subtilis and Pseudomonas aeruginosa with high effectiveness (low minimum inhibitory concentration [MIC] value) 40 and 60 μg/mL, respectively.     

Synthesis and reactions of some new allyl furobenzopyranone derivatives

Reaction of visnaginone 1 with allyl bromide gave O‐allyl visnaginone 2 which underwent Claisen rearrangement to yield 7‐allylbenzofuran derivative 3 . Reaction of 3 with different aromatic aldehydes gave the corresponding 5‐cinnamoylbenzofuran derivatives 4a‐d . Condensation of the latter chalcones 4a,c,d with hydrazine hydrate and phenylhydrazine provided, the corresponding pyrazoline derivatives 7a‐f . Claisen condensation of compound 3 with ethyl acetate and diethyl carbonate afforded Claisen adducts 8 and 12 which easily cyclized to 9 and 13 , which are endowed with interesting biological properties.     

Study on the murexide reaction. V

Although the reaction of caffeine with hydrogen peroxide/hydrochloric acid or nitric acid and then with ammonia has been known to give a purple coloration (Murexide reaction), the use of hydrazine instead of ammonia is found to provide no purple coloration. The reaction of caffeine with hydrogen peroxide/hydrochloric acid and then with hydrazine hydrate afforded a yellow reaction mixture, from which 4-methyl-6-(N-methylcarbamoyl)-3,5-dioxo-2,3,4,5-tetrahydrotriazine 9 , oxalyl hydrazide 10 and hydroxylamine hydrochloride were isolated. The reaction of caffeine with nitric acid and then with hydrazine hydrate furnished a yellow reaction mixture, from which 8-amino-1,3,7-trimethyl-2,6-dioxo-1H,3H,7H-xanthine 11, 9 and hydroxylamine nitrate were isolated. Compound 9 was clarified to be produced from 3-hydroxy-4,6-dimethyloxazolo[4,5-d]pyrimidine-2,5,7(3H,4H,6H)-trione 3 and 1,3-dimethylalloxan 7 by the ring transformation with hydrazine.     

Intramolecular Amidation: Synthesis of Novel Thiazole‐Fused Diazepinones

A new class of thiazole‐fused diazepinones has been synthesized by the application of intramolecular hydrazonolysis, wherein 2‐arylamino‐4‐coumarinyl‐5‐formyl thiazoles were treated with hydrazine hydrate in refluxing ethanol to yield the rearranged products via an interesting ring‐opening and cyclization process.     

Synthesis of Some Novel N-Substituted Phthalazinone and Pyridopyridazinone Derivatives

Phthalazinone and pyridopyridazinone derivatives 3, 5, and 9 were prepared via reaction ofappropriate lactams 2 and 8 with 2-bromoethylphthalimide, N-tosylaziridine, and N,O-ditosyl derivatives of N-methylethanolamine in a two-step process in the presence of MeONa/MeOH or NaH/dimethylformamide (DMF). Starting compounds 2 and 8 were obtained by reaction of hydrazine hydrate with isoindolinones 1 or azaisoindolinones 6. Selected N-(2-phthalimidoethyl)-phthalazinones were converted into corresponding 2-[2-(methylamino) ethyl]- derivatives in satisfactory yields by treatment with hydrazine.