Reaction of methyl 1-bromocyclopentane- and 1-bromocyclohexanecarboxylates with zinc and 2-arylmethylidene-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-inden-1-ones or 2-arylmethylidene-3,4-dihydronaphthalen-1(2<Emphasis Type="Italic">H</Emphasis>)-ones

Methyl 1-bromocyclopentanecarboxylate and methyl 1-bromocyclohexanecarboxylate reacted with zinc and 2-arylmethylidene-2,3-dihydro-1H-inden-1-ones or 2-arylmethylidene-3,4-dihydronaphthalen-1(2H)-ones to give 4′-aryl-4′,5′-dihydro-2′H-spiro[cyclopentane(cyclohexane)-1,3′-indeno[1,2-b]pyran]-2′-ones or 4-aryl-5,6-dihydrospiro[benzo[h]chromene-3,1′-cyclopentane(cyclohexane)]-2(4H)-ones, respectively.     

Convenient preparation of N-substituted 2-amino-4H-3,l-benzoxazin-4-ones and 3-substituted 2,4(1H,3H)-quinazolinediones

Room temperature treatment of 2-(3-arylureido)benzoic acids ( 1 ) and methyl 2-(3-alkyl-, or 3-arylureido)- benzoates ( 2 ) with concentrated sulfuric acid leads to N-substituted 2-amino-4H-3,l-benzoxazin-4-ones ( 3 ) in generally very good yields. The isomeric 3-substituted 2,4(1H,3H)-quinazolinediones ( 4 ) are conveniently made in high yield by the action of aqueous-ethanolic sodium hydoxide on 2.     

The synthesis of methyl 2-(benzyloxycarbonyl)amino-3-dimethylaminopropenoate. The synthesis of trisubstituted pyrroles, 3-amino-2H-pyran-2-ones,fused 2H-pyran-2-ones and 4H-pyridin-4-ones

Methyl 2-(benzyloxycarbonyl)aimno-3-dimemylaminopropenoate ( 2 ) was prepared from methyl N-(benzyloxycarbonyl)glycinate ( 1 ) and t-butoxybis(dimethylamino)methane, and used as a reagent for preparation of substituted 3-(benzyloxycarbonyl)amino-4H-quinolizin-4-ones 5 and 6 , ?2H-pyran-2-ones 17–19 , ?2H-1-benzopyran-2-ones 28–31 , and -naphthopyrans 32–35 , ?2H-pyrano[3,2-c]pyridine-2,5-dione 46 , -pyrano-[4,3-b]pyran-2,5-dione 47 , -pyrano[3,2-c]benzopyran-2,5-dione 48 , -pyrano[2,3-c]pyrazol-6-ones 49 and 50 , -pyrano[2,3-d]pyrirnidin-7-ones 51 and 52 derivatives. In the reaction of 2 with 1,3-diketones trisubsti tuted pyrroles 14–16 were formed. Selective removal of benzyloxycarbonyl group was achieved by cat alytic transfer hydrogenation with Pd/C in the presence of cyclohexene to afford free 3-amino compounds 7 , 8 , 20 , 36–38 and 53–57 in yields better than 80%.     

Photoisomerization of 2H,6H-thiin-3-one 1-oxides to 3H,7H-[1,2]oxathiepin-4-ones

Oxidation of 2H, 6H-thiin-3-ones 1a – c with 3-chloroperbenzoic acid affords the corresponding 1-oxides 2a – c . On irradiation (350 nm) in either benzene or MeCN, these cyclic sulfoxides 2 isomerize to 3H, 7H-1,2-oxathiepin-4-ones 3 . The tetramethyl derivative 3a is isolated by flash chromatography at ?10°, but, at higher temperatures, it undergoes ring contraction and H₂O elimination to give 4,4-dimethyl-2(2-methylprop-2enylidene)thietan-3-one ( 4 ). Diemthyloxathiepinones 3b and 3c undergo ring contraction in MeOH to afford 1-(4-methylthiophen-2-yl)ethanone ( 5 ) and two diastereoisomeric 4,4-dimethyl-2-methoxy-2-(1-methoxyethyl)thietan-3-ones ( 6 and 7 , respectively).     

A new preparation of substituted 4H-1-benzothiopyran-4-ones from c(α)N-benzoylhydrazones or c(α)N-carboalkoxyhydrazones and methyl thiosalicylate

C(α)N-Benzoylhydrazones or C(α),N-carboalkoxyhydrazones were dilithiated with excess lithium diisopropylamide, and the dianion-type intermediates were condensed with lithiated methyl thiosalicylate, followed by cyclization/hydrolysis to substituted 4H-1-benzothiopyran-4-ones (thioflavones/thiochromones).     

Heterocyclic compounds from 3,3-dimercapto-1-aryl-2-propen-1-ones. Note 1. 4-Ary1-1,3-dihydro-2H-1,5-benzodiazepine-2-thiones

A series of new 4-aryl-1,3-dihydro-2H-1,5-benzodiazepine-2-thiones ( 3 ) has been synthesized by condensing the 3,3-dimercapto-1-aryl-2-propen-1-ones with o-phenylenediamine. The structure was established by the results of acid cleavage and by nmr spectra. The alkylation of compounds 3 gave 2-alkylthio-4-aryl-3H-1,5 benzodiazepines ( 10 ).     

α-pyrones. III Synthesis of 5,6-dihydro-1H-benzo[c]-quinolizin-1-ones from 6-(2-nitrostyryl)-2H-pyran-2-ones

The 6-(2-nitrostyryl)-2H-pyran-2-ones 1 were reduced with hydrogen over Pd/C at room temperature and atmospheric pressure giving the 2-benzoylamino-4-(1,2,3,4-tetrahydro-2-quinolinylidene-2-pentenedioic acid derivatives 2 which were converted, without isolation, into the 5,6-dihydro-1H-benzo[c]quinolizin-1-ones 4 in refluxing acetic anhydride. When α-aminoacids 2 were treated with acetic anhydride at room temperature oxazolones 3 were isolated, while by heating quinolizines 4 were found. Compounds 3 were transformed into 4 in refluxing acetic acid or anhydride.     

A facile and novel synthesis of 1,6-naphthyridin-2(1H)-ones

A new and convenient procedure for the synthesis of 1,6-naphthyridin-2(1H)-ones and their derivatives is described. In the first scheme 5-acetyl-6-[2-(dimethylamino)ethenyl]-1,2-dihydro-2-oxo-3-pyridinecarbonitrile ( 4 ) obtained by the reaction of N,N-dimethylformamide dimethyl acetal with 5-acetyl-1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile ( 3 ) was cyclized to 1,2-dihydro-5-methyl-2-oxo-1,6-naphthyridine-3-carbonitrile ( 5 ) by the action of ammonium acetate. Thermal decarboxylation of acid 7 obtained from the hydrolysis of nitrile 5 led to a mixture of 5-methyl-1,6-naphthyridin-2(1H)-one ( 8 ) and its dimer 9 . Hydrazide 11 obtained from nitrile 5 in two steps was converted to 3-amino-5-methyl-1,6-naphthyridin-2(1H)-one ( 12 ) by the Curtius rearrangement. The amino group of 12 was readily replaced by treatment with aqueous sodium hydroxide to yield 3-hydroxy-5-methyl-1,6-naphthyridin-2(1H)-one ( 13 ). In the second scheme, Michael reaction of enamines of type 20 with methyl propiolate, followed by ring closure gave 5-acyl(aroyl)-6-methyl-2(1H)-pyridinones ( 21 ) which in turn were treated with Bredereck's reagent to produce 5-acyl(aroyl)-6-[2-(dimethylamino)ethenyl]-2(1H)-pyridinones ( 22 ). Treatment of 22 with ammonium acetate led to the formation of 1,6-naphthyridin-2(1H)-ones 23 .     

Selective synthesis of some 5-hydrazono-5,6,7,8-tetrahydro-2H-1-benzopyran-2-ones

A simple, highly selective transformation of 5,6,7,8-tetrahydro-2H-1-benzopyran-2,5-diones 1–3 and 14 with some phenylhydrazines and heterocyclic hydrazines to 5-hydrazono-2H-1-benzopyran-2-ones 4–12 and 15–16 is described. Under more severe conditions the hydrazonoquinoline derivative 17 was obtained from the benzopyran derivative 3 and Phenylhydrazine.     

Synthetic studies toward 4H-1,3-benzodioxin-2-ones

The investigation into the synthesis of 4H-1,3-benzodioxin-2-ones, utilizing the corresponding 2-(hydroxy-methyl)phenol as the starting diol, is described. The results illustrate that the synthesis of 4H-1,3-benzodi-oxin-2-ones can be achieved utilizing carefully controlled reaction conditions, in a 3–15% yield.     

A facile synthesis of 4-aryl-2H-1-benzopyran-2-ones

Reaction of 2-hydroxybenzophenones (1,3,7,8) with ethoxycarbonyl-methylenetriphenylphosphorane affords 4-aryl-2H-1-benzopyran-2-ones (2,4–6) in excellent yields.

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Eine einfache Synthese für 4-Aryl-2H-1-benzopyran-2-one

Zusammenfassung Die Reaktion der 2-Hydroxybenzophenone1,3,7 und8 mit Ethoxycarbonyl-methylentriphenylphosphoran ergab die 4-Aryl-2H-1-benzopyran-2-one2 und4–6 in ausgezeichneten Ausbeuten.

     

The synthesis of 5-substituted 3-benzoylamino-6-(2-substituted amino-1-ethenyl)-2H-pyran-2-ones and their transformations into 2H-pyrano[3,2-c]pyridine derivatives

A new approach to the 2H-pyrano[3,2-c]pyridine system is described. 5,6-Disubstituted 3-benzoylamino-2H-pyran-2-ones 3a,b , prepared from the corresponding 1,3-dicarbonyl compounds 1a,b and methyl (Z)-2-benzoylamino-3-dimethylaminopropenoate ( 2 ), were converted into 3-benzoylamino-6-(2-dimethylamino-1-ethenyl)-5-ethoxycarbonyl-2H-pyran-2-one ( 4a ) and 5-acetyl derivative 4b . The exchange of the dimethylamino group in 4a,b with aromatic amines 5a-f,m , héteroaromatic amines 5g-i , and benzylamines 5j-l produced 5-ethoxycarbonyl-3-benzoylamino-6-(2-arylamino- or heteroarylamino-or benzylamino-1-ethenyl)-2H-pyran-2-ones 6a-l , and its 5-acetyl analog 6m . The compounds 6 were cyclized in basic media into 2H-pyrano[3,2-c]pyridine derivatives 7a-h . Analogously react also α-amino acid derivatives 8a-c and 11 as nitrogen nucleophiles producing 9a-c, 10 and 12 .     

Synthesis of-4-((4-trimethylsilyl-1H-1,2,3-triazol-1-yl)methyl)-2H-chromen-2-ones: A novel class of heteroaryl anionic synthon

A one-pot synthesis of some novel anionic scaffolds: the substituted-4-((4-trimethylsilyl-1H-1,2,3-triazol-1-yl)methyl)-2H-chromen-2-one is reported. Reaction of 10 different substituted bromomethylcoumarins with trimethylsilylacetylene and sodium azide in the presence of copper(I) iodide catalyst gave the corresponding heteroaryl conjugates: the substituted-4-((4-trimethylsilyl-1H-1,2,3-triazol-1-yl)methyl)-2H-chromen-2-one in 70–92% yields. The structures of the synthesized compounds have been completely characterized by spectral and elemental analyses. For the first time, the representative single-crystal X-ray structure analysis of 6-methoxy-4-((4-trimethylsilyl-1H-1,2,3-triazol-1-yl)methyl)-2H-chromen-2-one is reported which confirms the formation of anionic synthon which bears the trimethylsilyl-group.     

Synthesis of novel dihydro-2H-1,2,4-oxadiazin-5(6H)-ones

The title compounds 4 were synthesized via the acid-catalyzed reaction of α-(acylaminooxy)carboxylic acid amides 6 with carbonyl compounds, and controlled catalytic hydrogenation of the resulting 2-benzyloxy-carbonyldihydro-2H-1,2,4-oxadiazin-5(6H)-ones 7 (R⁶ = PhCH₂O).     

Synthesis and properties of 5-aroylamino-2H-1,2,4-thiadiazol-3-ones

5 -Aroylamino-2H-1,2,4-thiadiazol-3-ones 3 were obtained from the corresponding 1-aroyl-2-thiobiurets 2 by oxidative cyclization with bromine. 5 -Aroylamino-2H-1,2,4-thiadiazol-3-ones 3 can exist in two tautomeric forms a lactam form and a lactim form. On the basis of the ¹³C nmr spectra and additional experimental information, it has been established that the stable form, in which these compounds exist, is the lactam form.     

Preparation of ethyl 1-hydroxy-2-naphthoates from 1H-2-benzopyran-1-ones: A new method

Lithio ethyl acetate is a superior reagent for the transformation of 1H-2-benzopyran-1-ones to naphthoates.     

Synthesis of pyrimidino[4,5-b][1,5]benzodiazepin-2-ones and pyrimidino[1,6-a]benzimidazol-1-ones from 4-ethoxycarbonylamino-1H-1,5-benzodiazpine-3-carbonitrile via 4-(2-aminoanilino)pyrimidin-2(1H)-one-5-carbonitriles

Reactions of 4-ethoxycarbonylamino-1H-1,5-benzodiazepine-3-carbonitrile (2) with aliphatic primary amines gave 1-substituted 4-(2-aminoanilino)pyrimidin-2(1H)-one-5-carbonitriles 3. Analogous reactions of 2 with aromatic primary amines afforded 2-(2′-anilino-1′-cyanovinyl)benzimidazoles 5 and 6. Upon treatment with triethylamine, 3 underwent intramolecular cyclization to give 3-substituted 5-aminopyrimidino[4,5-b]-[1,5]benzodiazepin-2(3H,11H)-ones 8 . Heating of 3 with p-toluenesulfonic acid in ethanol gave 2-substituted pyrimidino[1,6-a]benzimidazol-1(2H)one-4-carbonitriles 9 . Reactions of 2 with hydrazines were also described. Mechanistic pathways are proposed to account for the products.     

4-Substituted-3,4-dihydro-3-methyl-2H-1,3-benzoxazin-2-ones. III (2,3). Solvolytic-reductive transformation of 4-(2-keto)-benzoxazin-2-ones into oxazin-2-ones

A series of 4-(2-keto-substituted)-3,4-dihydro-3-methyl-2H-1,3-benzoxazin-2-ones 1 (Table I) was synthesized by condensation of 3-alkyl-3,4-dihydro-4-hydroxy-2H-1,3-benzoxazin-2-ones 4 with ketones 5 having active alpha hydrogens. In the presence of alcoholic potassium borohydride, compounds 1 underwent reductive transacylation to give 1,3-oxazin-2-one derivatives 3 (Table III, a,b,c). When the other side of the ketone possessed substituents other than hydrogen, there were always also normal reduction products, i.e., secondary alcohols 2 (Table II) in addition to 3.     

Reactions of methyl 3,3,3-trifluoro-2-(pyridin-2-ylimino)-propanoates with mono- and difunctional nucleophiles

Reactions of methyl 3,3,3-trifluoro-2-(pyridin-2-ylimino)propanoates with such nucleophiles and 1,3-binucleophiles as methanol, p-toluidine, phenylhydrazine, diethyl phosphonate, 2-aminobut-2-enenitrile, benzamidine, and 4,5-dihydro-1,3-thiazol-2-amine led to the formation of various acyclic 2-substituted methyl 3,3,3-trifluoro-2-(pyridin-2-ylamino)propanoates and trifluoromethyl-containing heterocyclic N-substituted 2-aminopyridine derivatives: 4,5-dihydro-1H-pyrroles, 4,5-dihydro-1H-imidazol-5-ones, and 2,3-dihydro-6Himidazo[2,1-b][1,3]thiazol-5-ones.     

Synthesis of 3-substituted 4H-1-benzothiopyran-4-ones

3-Substituted 2-phenyl-4H-1-benzothiopyran-4-ones (thioflavones) were prepared to test antimicrobial activity. It was found that 3-(phenyl)thiochromone derivatives (isothioflavones) were prepared by the Meerwein reaction of thiochromone with p-nitrobenzenediazonium ion. 3-(Formyl)thioflavone exhibits weak antimicrobial activity against Trichophytons and Candida.