Unambiguously confirmed structure of 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one

To determine the structures of two isomeric products, 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (2) and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (3) obtained by condensation of 2,3-diaminopyridine (1) with ethyl benzoylpyruvate [1–3], these compounds were hydrolyzed to give 2-methyl-4H-pyrido[2,3-b]pyrazin-3-one (4) and 3-methyl-1H-pyrido[2,3-b]pyrazin-2-one (5) , respectively [4,5]. Both hydrolysates 4 and 5 were hydrogenated to afford 2-methyl-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (6) and 3-methyl-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (7) . The latter compound was identical with an unequivocally synthesized compound providing proof for the structures of all these compounds.     

Heterocycles structurally influenced by a side chain. X. Effect of temperature and side chain on the imine-enamine tautomerism in the quinoxalinone and pyridopyrazinone systems

3-(1-Benzoyl)ethyl-1H-pyrido[2,3-b]pyrazin-2-one ( 7 ), 3-(1-ethoxycarbonyl)ethyl-1H-pyrido[2,3-b]-pyrazin-2-one ( 8 ), and 3-(1-benzoyl)ethyl-1H-quinoxalin-2-one ( 9 ) exist only in the imine form due to the steric effect of the methyl substituent. As regards the imine-enamine tautomerism, 3-(β-carbonylmethylene) derivatives of 1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one such as 12 and 15–18 gradually change from the enamine form to the imine form with elevated temperatures; however, 3-(carbonylmethylene) derivatives of 3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one such as 10, 19 and 20 show little temperature effect. 2-Phenacylidene-1,2-dihydro-4H-pyrido[3,4-b]pyrazin-3-one ( 21 ) and 3-phenacylidene-3,4-dihydro-1H-pyrido[3,4-b]pyrazin-2-one ( 22 ), which exist in the enamine form, show no temperature effect.     

Synthesis of a rotenone-like benzopyranobenzopyranone

The synthesis of a novel rotenone-like molecule, 9-methoxy-8-methyl-6,6a,12,12a-tetrahydro[1]benzopyrano-[3,4-b][1]benzopyran-12-one ( 2 ) is described. Efficient syntheses of 3,4-dihydro-2H-[1]benzopyran-3-one ( 9 ) from ethyl 3-hydroxy-2H-[1]benzopyran-4-carboxylate ( 6 ), an intermediate in the synthesis of 2 , were developed. Thermolysis of 6 and 9 in decalin yielded 6,8-dihydro-14H-bis[1]benzopyrano[3,4-b:4′,3′-e]pyran-14-one ( 8 ), which has previously been described. Also produced in the thermolysis was the isomeric 1H-bis[1]-benzopyrano[3,4-b:3′,4′-á]pyran-7-(9H)one ( 10 ), the first member of a novel, pentacyclic ring system.     

Nitrogen bridgehead compounds. Part 86. Synthesis and reactivity of 7,12-dihydropyrimido[1′,2′;1,2]pyrido[3,4-b]indol-4(6H)-ones. Debenzologues of rutaecarpine alkaloids

A series of 7,12-dihydropyrimido[1′2′:1,2]pyrido[3,4-b]mdole-4(6H)-ones was prepared by Fischer indolization of 9-arylhydrazono-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrirmdin-4-ones. Quantum chemical calculations (ab initio and AM1) indicate that position 3 of 7,12-dihydropyrimido[1′,2′:1,2]pyrido-[3,4-b]indole-4(6H)-one can be involved in electrophilic substitutions, while position 2 is sensitive towards nucleophilic attack. Bromination of 6-methyl-7,12-tetrahydropyrimido[1′,2′:1,2]pyrido-[3,4-b]indol-4(6H)-one 16 with bromine afforded 3-bromo derivative 25 , which was reacted with cyclic amines to give 2-ammo-7,12-dihydropyrirmdo[1′2′:1,2]pyrido[3,4-b]indol-4(6H)-ones 26–30 in an addition-elimination reaction. Vielsmeier-Haack formylation of compound 16 gave 12-formyl 31 and 3,12-diformyl 32 derivatives (an N-formyl-1-deaza derivative of nauclefidine alkaloid 34 ) at 60° and 100°, respectively. 3,12-Diformyl compound 32 was oxidized to 3-carboxyl derivative 33 with potassium permanganate. The quaternary salt 35 , obtained from compound 16 with dimethyl sulfate, suffered a ring opening on the action of aqueous sodium hydroxide. The new compounds have been characterized by elemental analyses uv, ¹H nmr and in some cases by ¹³C ruler, CD spectra and X-ray investigations.     

Isatins 3-C annulation vs ring-opening: Two different pathways for synthesis of spiro compounds via multicomponent reactions

An efficient synthesis of spiro compounds via two different pathways from the reactions of isatins, 3-phenylisoxazol-5(4H)-one (3-ethylisoxazol-5(4H)-one), and pyrazol-5-amine (6-aminopyrimidine-2,4(1H,3H)-dione) were reported. The catalyst Amberlyst-15 could be easy recycled and reused for many time without any appreciable loss in catalytic activity. The new type spiro compounds were gained through the ring-opening of isatins process. The structures of spiro[indoline-3,4′-isoxazolo[5,4-b]pyrazolo[4,3-e]pyridin]-2-one, spiro[isoxazolo[5,4-b]quino line-4,5′-pyrrolo[2,3-d]pyrimidine]-2′,4′,6′(1′H,3′H,7′H)-trione, and spiro[indoline-3,4′-pyrazolo[3,4-b]pyridine]-2,6′(5′H)-dione were successfully confirmed by ¹H NMR, ¹³C NMR, HRMS, and X-ray crystal diffraction analysis.     

Condensed benzopyrans III. 3H,4H[1] benzopyrano [3,4-b] pyrrol-4-ones

The diazotization of 3-aminocoumarin followed by its reduction gave the cournarin-3-yl-hydrazine which, without isolation, reacted with various carbonyl compounds in a Fisher's indohzation reaction to give derivatives (Ib-Ih) of the yet unreported system 3H,4H[1]benzopyrano[3,4-b]pyrrol-4-one.     

Thiophene systems. 13. The synthesis of novel thienopyranones

The syntheses and spectral properties of novel dimethyl-substituted thieno[3,2-b]-, [3,4-b]- and [2,3-b]pyran-ones are described. The uv spectra of the three systems are distinctly different as supported by HOMO/LUMO calculations. 5,6-Dihydro-5,5-dimethyl-7H-thieno[3,4-b]pyran-7-one ( 10 ) and 5,6-dihydro-6,6-dimethyl-4H-thieno[2,3-b]pyran-4-one ( 20 ) represent the first members of these thienopyranone ring systems.     

Azaindoles. V. Pyrido(4,3-b]indoles (γ-carbolines) fonctionnalisés sur leur sommet 4: Synthèse en une seule étape

In boiling diphenylether phenylhydrazine reacts with 1,2-dihydro-2-oxo-4-hydroxypyridines to give 3,4-dihydro-4-oxo(9H)-pyrido[4,3-b]indoles (γ-carbolines) in one step. Nucleophilic displacement of their 4-chloro derivatives by secondary amines affords both 3,4-disubstituted γ-carbolines and chlorination of 2,3-dimethyl-4-oxo(9H)pyrido[4,3-b]indoles, as well as methylation of 2-methyl-4-chloro-(9H)pyrido[4,3-b]indole leads to derivatives in the (3H)4-substituted pyrido[4,3-b] indole series.     

A convenient synthesis of (z)-3-(α-alkoxycarbonyl-α-cyanomethylene)-2-oxo-1,2,3,4-tetrahydroquinoxalines and related compounds

(Z)-3-(α-Alkoxycarbonyl-α-cyanomethylene)-2-oxo-1,2,3,4-tetrahydroquinoxalines 3 and (Z)-3-(α-alkoxycarbonyl-α-cyanomethylene)-3,4-dihydrobenzo[g]quinoxalin-2(1H)-ones 5 possessing various alkoxycarbonyl groups were prepared in good yields directly from the reaction of dialkyl (E)-2,3-dicyanobutendioates 1 with o-phenylenediamine ( 2 ) or with 2,3-diaminonaphthalene ( 4 ), respectively. Furthermore, 2,3-diaminopyridine ( 6 ) and 3,4-diaminopyridine ( 7 ) were reacted with the diethyl ester 1b to give (Z)-2-(α-cyano-α-ethoxycarbonylmethylene)-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one ( 8 ) and (Z)-3-(α-cyano-α-ethoxycarbonylmethylene)-3,4-dihydro-1H-pyrido[3,4-b]pyrazin-2-one ( 9 ), respectively. The structural studies of 3, 5, 8 , and 9 were carried out by nmr experiments in some details.     

2,2′-Bifurylidene-5,5′-diones,Coumarins, 3a, 7a-dihydro-1H-inden-1-ones,and 5H-furo[3,2-b]pyran-5-ones from propyne and carbon monoxide

The [Co₂ (CO)₈]-catalyzed reaction between propyne and CO in acetone at 110° and 170 bar was re-investigated. There are five major products: (E)-3,4′-dimethyl-2,2′-bifurylidene-5,5′-dione ( 4 ), 3,5,8-trimethylcoumarin ( 8 ), 3a, 7a-dihydro-2,4,7,7a-tetramethyl-1H-inden-1-one ( 9 ), 2,6-dimethyl-5H-furo [3,2, -b]- pyran-5-one ( 11 ), and 2,7-dimethyl-5H-furo 3,2-b-pyran-5-one ( 12 ); of these, only one, 4 . had previously been recognized. In parallel experiments were obtained 2,6-dipentyl-5 H-furo[3,2-b]pyran-5-one ( 13 ), 2,7-dipentyl–5H-furo[3,2-b]pyran-5-one ( 14 ), 3a, 7a-dihydro-2,4,7,7a-tetrapentyl-1H-inden-1-one ( 15 ). And 3a, 7a-dihydro-2,4,6,7a-tetrapentyl-1H-inden-1-one ( 16 ) from hept-1-yne, and two further types of products from two atypical 1-alkynes: 3,6,9-tri(tert-butyl)-1-oxaspiro[4.4]nona-3,6,8-trien-2-one ( 20 ) from (tert-butyl)acetylene and the exo-dimer 21 of 2,5-bis(trimethylsilyl)cyclopenta-2,4-dien-1-one ( 22 ) from (trimethylsilyl)acetylene. Compounds 11,12 , and 20 were identified by X-ray analysis.     

Cyclofunctionalization of 6-alkenylsulfanylpyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]-pyrimidin-4(5<Emphasis Type="Italic">H</Emphasis>)-ones with arenesulfenyl chlorides

Reactions of 6-allylsulfanylpyrazolo[3,4-d]pyrimidin-4(5H)-one with arenesulfenyl chlorides in chloroform gave products of addition of the latter at the exocyclic double bond, while analogous reactions in acetic acid in the presence of LiClO₄ were accompanied by intramolecular electrophilic cyclization involving the N⁷ atom. 6-Cinnamylsulfanylpyrazolo[3,4-d]pyrimidin-4(5H)-one reacted with arenesulfenyl chlorides in acetic acid in the absence of electrolyte to produce fused pyrazolo[4′,3′: 5,6]pyrimido[2,1-b][1,3]thiazine derivatives. Introduction of a bulky phenyl group into position 1 of the pyrazolo[3,4-d]pyrimidine system reduces the yield of the corresponding intramolecular cyclization product at N⁷ as a result of concurrent formation of acyclic addition product. DOI     

Synthesis and structure of 2-phenylanthra[9,1-<Emphasis Type="Italic">bc</Emphasis>]pyrrol-6-one

Reduction of anti-1-benzoylanthraquinone oxime gave 2-phenylanthra[9,1-bc]pyrrol-6-one whose structure was determined by X-ray analysis. The molecule of 2-phenylanthra[9,1-bc]pyrrol-6-one is almost planar, and its crystalline structure is characterized by head-to-tail chains formed via intermolecular hydrogen bonds N-H ... O.     

Synthesis of certain 3-alkoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidines structurally related to adenosine,inosine and guanosine

Several 3-alkoxysubstituted pyrazolo[3,4-d]pyrimidine ribonucleosides structurally related to adenosine, inosine and guanosine have been prepared by the direct glycosylation of preformed aglycon precursor containing a 3-alkoxy substituent. Ring closure of 5(3)-amino-3(5)-ethoxypyrazole-4-carboxamide ( 6b ) with either formamide or potassium ethyl xanthate gave 3-ethoxyallopurinol ( 7b ) and 3-ethoxy-6-thioxopyrazolo[3,4-d]-pyrimidin-4(5H,7H)-one ( 10 ), respectively. Methylation of 10 gave the corresponding 6-methylthio derivative 15 . Similar ring annulation of 5(3)-methoxypyrazole-4-carboxamide ( 6a ) with formamide afforded 3-methoxyallopurinol ( 7a ). Treatment of 5(3)-amino-3(5)-methoxypyrazole-4-carbonitrile ( 5a ) with formamidine acetate furnished 4-amino-3-methoxypyrazolo[3,4-d]pyrimidine ( 4 ). High-temperature glycosylation of 7b with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the presence of boron trifluoride etherate gave a 2:1 mixture of N-1 and N-2 glycosyl blocked nucleosides 11b and 13b . Deprotection of 11b and 13b with sodium methoxide gave 3-ethoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4(5H)-one ( 12b ) and the corresponding N-2 glycosyl isomer 14b , respectively. Similar glycosylation of either 4 or 7a , and subsequent debenzoylation gave exclusively 4-amino-3-methoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidine ( 9 ) and 3-methoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4-(5H)-one ( 12a ), respectively. The structural assignment of 12a was made on the basis of single-crystal X-ray analysis. Application of this general glycosylation procedure to 15 gave the corresponding N-1 glycosyl derivative 16 as the sole product, which on debenzoylation afforded 3-ethoxy-6-(methylthio)-1-(3-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4(5H)-one ( 17 ). Oxidation of 16 and subsequent ammonolysis furnished the guanosine analog 6-arnino-3-ethoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]-pyrimidin-4(5H)-one ( 19 ). Similarly, starting from 3-methoxy-4,6-bis(methylthio)pyrazolo[3,4-d]pyrimidine ( 20 ), 6-amino-3-methoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4(5H)-one ( 23 ) was prepared.     

Nitrogen bridgehead compounds. Part 85. Synthesis and reactivity of 3,4-dihydro-1H,6H[1,4]oxazino[3,4-b]quinazolin-6-ones

3,4-Dihydro-1H,6H-[1,4]oxazino[3,4-b]quinazolin-6-one 3 and its 1-methyl and 1-hydroxy derivatives 8 and 13 were prepared by different routes. The active methylene group of compound 3 was reacted with electro-hilic reagents (bromine, phenyldiazonium chloride, nitrous acid, a Vielsmeier-Haack reagent, aromatic aldehydes and diethyl oxalate) to yield 1-substituted-3,4-dihydro[1H,6H)-1,4-oxazino[3,4-b]quinazo-lin-6-ones. The reactivity of 1-hydroxy and 1-bromo derivatives 13 and 15 were also investigated in some reactions. The 3,4-dihydro-lH,6H-[1,4]oxazino[3,4-b]quinazolin-6-ones were characterized by means of uv, ¹H and ¹³C nmr spectroscopy.     

Reaction of β-arylidennaphthylamines with 4-hydroxycoumarin. A correction in structural assignment of the product. III

The reaction of 4-hydroxycoumarin with β-arylidennaphthylamines constitutes a convenient synthetic route to the hitherto unknown 2H-benzo[f][1]benzopyrano[4,3-b]quinolin-2-one, VI . The X-ray crystallography data conform with the present benzopyrano[4,3-b]quinolin-2-one ring system and disprove the benzopyrano[3,4-c]quinolin-2-one structure previously assigned for such reaction products.     

Electrophilic heterocyclization of 6-alken(yn)ylsulfanyl-pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(5<Emphasis Type="Italic">H</Emphasis>)-ones

6-Allylsulfanyl-1-arylpyrazolo[3,4-d]pyrimidin-4(5H)-ones react with iodine and sulfuric acid to give angular pyrazolothiazolopyrimidine derivatives. The reaction of 6-(prop-2-yn-1-ylsulfanyl)-1-(4-tolyl)-pyrazolo[3,4-d]pyrimidin-4(5H)-one with sulfuric acid gives angularly fused pyrazolo[4,3-e][1,3]thiazolo-[3,2-a]pyrimidin-4-one, whereas in the reaction with sodium methoxide linearly fused pyrazolo[3,4-d][1,3]-thiazolo[3,2-a]pyrimidin-4-one was formed. Linearly fused pyrazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazole derivatives were also obtained by reaction of 1-aryl-6-(3-phenylprop-2-en-1-ylsulfanyl)pyrazolo[3,4-d]pyrimidin-4(5H)-ones with sulfuric acid.     

Building libraries of skeletally diverse scaffolds from novel heterocyclic active methylene compound through multi-component reactions

Libraries of skeletally diverse potential bioactive polycyclic/spirocyclic heterocyclic compounds; 2-amino-7,9-dimethyl-5-oxo-4-aryl-4,5,6,7-tetrahydropyrano[2,3-d]pyrazolo[3,4-b]pyridine-3-carbonitrile, 2′-amino-7′,9′-dimethyl-2,5′-dioxo-6′,7′-dihydro-5′H-spiro[indoline-3,4′-pyrano[2,3-d]pyrazolo[3,4-b]pyridine]-3′-carbonitrile, and 5,5′-(arylmethylene)bis(4-hydroxy-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one) have been synthesized through a multi-component reaction using novel heterocyclic active methylene compound 4-hydroxy-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-6(7H)-one as one of the building blocks. This protocol can be considered to be an efficient and eco-friendly strategy for diversity oriented synthesis.     

Synthesis of certain pyrazolo[3,4-d]pyrimidin-3-one nucleosides

Synthesis of the pyrazolo[3,4-d]pyrimidin-3-one congeners of guanosine, adenosine and inosine is described. Glycosylation of 3-methoxy-6-methylthio-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one ( 13 ) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose ( 16 ) in the presence of boron trifluoride etherate gave 3-methoxy-6-methylthio-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4(5H)-one ( 17 ) which, after successive treatments with 3-chloroperoxybenzoic acid and methanolic ammonia, afforded 6-amino-3-methoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4(5H)one ( 18 ). The guanosine analog, 6-amino-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidine-3,4(2H,5H)-dione ( 21 ), was made by sodium iodide-chlorotrimethylsilane treatment of 6-amino-3-methoxy-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4(5H)one ( 19 ), followed by sugar deprotection. Treatment of the adenine analog, 4-amino-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one ( 11 ), according to the high temperature glycosylation procedure yielded a mixture of N-1 and N-2 ribosyl-attached isomers. Deprotection of the individual isomers afforded 4-amino-3-hydroxy-1-βribofuranosylpyrazolo-[3,4-d]pyrimidine ( 26 ) and 4-amino-2-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-3(7H)-one ( 27 ). The structures of 26 and 27 were established by single crystal X-ray diffraction analysis. The inosine analog, 1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidine-3,4(2H,5H)-dione ( 28 ), was synthesized enzymatically by direct ribosylation of 1H-pyrazolo[3,4-d]pyrimidine-3,4(2H,5H)-dione ( 8 ) with ribose-1-phosphate in the presence of purine nucleoside phosphorylase, and also by deamination of 26 with adenosine deaminase.     

Etude de la décomposition thermique d'azido dithiényl-1,2 éthènes et éthanes

Thermal decomposition of azido-1,2-dithienylethenes 1 gave thienyl 4H-thieno[3,2-b]pyrroles 3 . For the 3,4-disubstituted thiophene derivatives 2 , the same reaction led to the amino-1,2-dithienylethenes 4 . In contrast, only azido-1,2-dithienylethanes 7 led to thienyl-5,6-dihydro-4H-thieno[3,4-b]pyrroles 8 . The structure of the obtained derivatives was established on the basis of ¹H nmr, ir, and mass spectral data.     

Benzofurano derivatives of coumarins as possible antifertility agents

Synthesis and medicinal importance of 4-methyl-6-nitro-8,9,10,11-tetrahydro-2H-benzofuro[2,3-b]-1-benzo-pyran-2-one (I), 4-ethyl-11-nitro-6,7,8,9-tetrahydro-2H-benzofuro[3,2-g]-1-benzopyran-2-one (II), and 6,7-di-hydro-4,13-dimethylbis-1-benzopyrano[6,7-d:7′,6′-d']-2H,11H-benzo[1,2-b:3,4-b']difuran-2,11-dione (III) is presented. The structures of these compounds were confirmed by elemental analysis and spectral studies.