Heating In Polyphosphoric Acid Research Articles

Synthesis of naphtho[1,2‐b]‐, naphtho[2,1‐b]‐, and naphtho[2,3‐b]azepinones via proton‐induced cyclization of N‐1(2)‐naphthyl styrylacetamides

AbstractOn heating in polyphosphoric acid, N‐1‐naphthyl styrylacetamides undergo proton‐induced intramolecular cyclization at position 2 of the naphthyl ring to provide 5‐aryl‐1,3,4,5‐tetrahydro‐2Н‐naphtho[1,2‐b]azepin‐2‐ones, while their N‐2‐naphthyl analogues, when similarly reacted, are cyclized at positions 1 and 3 of the naphthyl ring and at the amide nitrogen atom leading, respectively, to 1‐aryl‐1,2,3,5‐tetrahydro‐4Н‐naphtho[2,1‐b]azepin‐4‐ones, 5‐aryl‐1,3,4,5‐tetrahydro‐2Н‐naphtho[2,3‐b]azepin‐2‐ones, and 5‐aryl‐1‐(2‐naphthyl)pyrrolidin‐2‐ones.

Fused Pyrimidine Systems: XVII. Imidazo- and Pyrimidopyrido[3,2-d]pyrimidin-4(3H)-ones

2-(Allylamino)pyrido[3,2-d]pyrimidin-4(3H)-one was converted to linearly fused dihydroimidazo- [1,2-a]pyrido[3,2-d]pyrimidine on heating in polyphosphoric acid, whereas its reactions with molecular iodine and chlorosulfanylarenes afforded mainly angularly fused analogs. 2-(Cinnamylamino)pyrido[3,2-d]pyrimidin- 4(3H)-one reacted with polyphosphoric acid and chlorosulfanylarenes to give linear pyrido[3,2-d]pyrimido-[1,2-a]pyrimidinones, and its iodocyclization led to the formation of angularly fused derivative.

Formation of ω-(4-oxo-1,4-dihydropyridin-2-yl)alkanamides in the Beckmann rearrangement of spiro-fused cycloalkanone oximes

ω-(4-Oxo-1,4-dihydropyridin-2-yl)alkanamides were obtained from cycloalkanone oximes spirofused to 4-oxo-6-methyl-1,2,3,4-tetrahydropyridine fragment through the α-carbon atom and C2, respectively, on heating in polyphosphoric acid. The resulting amides were converted to the corresponding acids and methyl esters. Methylation of 5-(6-methyl-4-oxo-1,4-dihydropyridin-2-yl)pentanamide with diazomethane gave 4-methoxypyridine derivative as the major product and a small amount of N-methyl derivative, 5-(1,6-di-methyl- 4-oxo-1,4-dihydropyridin-2-yl)pentanamide.

Electrophilic intramolecular cyclization of functional derivatives of unsaturated compounds: VIII. Cyclization of 4-aryl-N-(thiophen-3-yl)but-3-enamides by the action of polyphosphoric acid and chlorosulfanylarenes

Intramolecular cyclization of 4-aryl-N-(thiophen-3-yl)but-3-enamides on heating in polyphosphoric acid afforded 8-aryl-4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-ones and 5-aryl-1-(thiophen-3-yl)pyrrolidin-2-ones. Cyclofunctionalization of the title compounds with (chlorosulfanyl)benzene and 4-(chlorosulfanyl)-toluene led to the formation of 8-aryl-7-arylsulfanyl-4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-ones or their mixtures with 5-aryl-4-arylsulfanyltetrahydrofuran-2-ones. 1-(Chlorosulfanyl)-4-nitrobenzene reacted with 4-(4-methylphenyl)-N-(thiophen-3-yl)but-3-enamide and 4-(4-fluorophenyl)-N-(thiophen-3-yl)but-3-enamide to give 5-(4-methylphenyl)-4-(4-nitrophenylsulfanyl)-1-(thiophen-3-yl)pyrrolidin-2-one and 5-(4-fluorophenyl)-4-(4-nitrophenylsulfanyl)tetrahydrofuran-2-one, respectively.

Fused pyrimidine systems: XVI. Electrophilic intramolecular cyclization of 2-(alkenylsulfanyl)pteridin-4(3H)-ones

2-[Allyl(but-3-en-1-yl, pent-4-en-1-yl)sulfanyl]pteridin-4(3Н)-ones at heating in polyphosphoric acid undergo an intramolecular cyclization affording respectively 9-methyl-8,9-dihydro-5H-[1,3]thiazolo[3,2-a] pteridin-5-one and 10-methyl(ethyl)-9,10-dihydro-5Н,8Н-[1,3]thiazino[3,2-a]pteridin-5-ones of angular structure. The cyclization of 2-(alkenylsulfanyl)pteridin-4(3Н)-ones under the action of iodine or arylsulfenyl chlorides afforded iodo(arylsulfanyl) derivatives of angularly fuzed thiazolo- and thiazinopteridines.

Synthesis of 3,13-dichlorobenzo[b]quino[4,3-h][1,6]naphthyridin-6(5H)-one derivatives from 2-oxoquinoline-3-carbonyl chloride and 2,6-dichloroquinolin-4-amine

The reaction of 2-oxo-1,2-dihydroquinoline-3-carbonyl chlorides and 2,6-dichloroquinolin-4-amine leads to the formation of N-(2,6-dichloroquinolin-4-yl)-2-oxo-1,2-dihydroquinoline-3-carboxamides. The latter is cyclized to fused [1,6]naphthyridine derivative – 3,13-dichlorobenzo[b]quino[4,3-h][1,6]naphthyridin-6(5H)-one, under heating in polyphosphoric acid at 150°C. The reaction sequence was generalized and was extended to synthetic derivatives. The structures of all synthesized compounds were confirmed by spectral data and elemental analysis.

Fused pyrimidine systems: XV. Intramolecular electrophilic cyclization of 2-allyl(propargyl, cinnamyl)amino-pyrido[2,3-d]pyrimidin-4(3H)-ones

2-(Allylamino)- and 2-(propargylamino)pyrido[2,3-d]pyrimidin-4(3H)-ones underwent intramolecular cyclization on heating in polyphosphoric acid to give angularly fused imidazo[1,2-a]pyrido[3,2-e]pyrimidin-5-ones. The cyclization of 2-(cinnamylamino)pyrido[2,3-d]pyrimidin-4(3H)-one under analogous conditions afforded linearly fused 4-phenyl-1,2,3,4-tetrahydro-6H-pyrido[2,3-d]pyrimido[1,2-a]pyrimidin-6-one. 2-(Allylamino)pyrido[2,3-d]pyrimidin-4(3H)-one reacted with iodine yielding 9-(iodomethyl)-8,9-dihydroimidazo[1,2-a]pyrido[3,2-e]pyrimidin-5(7H)-one as the major product, 2-(propargylamino)pyrido[2,3-d]pyrimidin-4(3H)-one gave rise to iodine addition product to the triple bond, and angularly fused 9-iodo-10-phenyl-7,8,9,10-tetrahydro-5H-pyrido[3,2-e]pyrimido[1,2-a]pyrimidin-5-one was obtained from the 2-(cinnamylamino) derivative. Electrophilic cyclization of 2-(allylamino)- and 2-(cinnamylamino)pyrido[2,3-d]pyrimidin-4(3H)-ones by the action of phenylsulfanyl chloride led to the formation of angularly fused 9-(phenylsulfanylmethyl)-8,9-dihydroimidazo[1,2-a]pyrido[3,2-e]pyrimidin-5(7H)-one and 10-phenyl-9-phenylsulfanyl-7,8,9,10-tetrahydro-5H-pyrido[3,2-e]pyrimido[1,2-a]pyrimidin-5-one.

Fused pyrimidine systems: XIII. Synthesis and some transformations of 1,3-thiazolo(thiazino)-fused pyrido[3,4-d]pyrimidines

2-[Allyl(propargyl)sulfanyl]pyrido[3,4-d]pyrimidin-4-ones at heating in polyphosphoric acid undergo an intramolecular cyclization with the formation of pyrido[4,3-e]thiazolo-[3,2-a]pyrimidin-5-ones of angular structure. Under similar conditions the cyclization of 2-(cinnamylsulfanyl)pyrido[3,4-d]-pyrimidin-4-one results in a linear pyrido[3′,4′:4,5]pyrimido-[2,1-b][1,3]thiazin-6-one. The iodocyclization of the same substrates affords the corresponding 9-(iodomethyl)(iodomethylidene)pyrido[4,3-e][1,3]thiazolo-[3,2-a]pyrimidin-5-ones and 3-iodopyrido[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-6-one of angular structure. 9-(Iodomethyl)-8,9-dihydro-5H-pyrido[4,3-e][1,3]thiazolo[3,2-a]pyrimidin-5-one treated with sodium azide gave 9-(azidomethyl) derivative whose cyclization with substituted alkynes in the presence of copper compounds provided pyrido [4,3-e][1,3]thiazolo[3,2-a]pyrimidinylmethyltriazoles.

Electrophilic intramolecular cyclization of functional derivatives of unsaturated compounds: V. Cyclization of anilides of styrylacetic acids in polyphosphoric acid

Anilides of styrylacetic acids at heating in polyphosphoric acid undergo an intramolecular cyclization giving 1,5-diarylpyrrolidin-2-ones, 5-aryl-1,3,4,5-tetrahydro-2H-benzazepin-2-ones, and 5-(3-fluorophenyl) dihydrofuran-2(3H)-one, where the ratio of the products depends on the character of the aromatic substituents in the amide and styrene fragments of the substrate.

Synthesis of new benzo[c]phenanthridine derivatives

Three-component condensation of naphthalen-1-amine with triethyl orthoformate and dimedone or cyclopentane-1,3-dione, as well as the reaction of naphthalen-1-amine with 2-acetyl-5,5-dimethylcyclohexane-1,3-dione, gave the corresponding 2-[1-(α-naphthylamino)alkylidene]cycloalkane-1,3-diones which underwent intramolecular cyclization to 7,8,9,10-tetrahydrobenzo[c]phenanthridin-7-one derivatives on heating in polyphosphoric acid. 9,9-Dimethyl-7,8,9,10-tetrahydrobenzo[c]phenanthridin-7-one was reduced to 9,9-dimethyl-7,8,9,10-tetrahydrobenzo[c]phenanthridin-7-ol with sodium tetrahydridoborate.

Synthesis of pyridines from alcohols in the system 1,3,5-triazine-polyphosphoric acid

We previously showed that the system 1,3,5-triazine–polyphosphoric acid (PPA) is an efficient reagent ensuring peri fusion of a pyridine ring to azaphenalenes [1, 2] and naphthalene-1,8-diamine [3]. The present communication reports on the reaction of alcohols Ia–Id with 1,3,5-triazine (III) on heating in PPA (prepared according to the procedure described in [4]; P2O5 concentration 86%), which leads to the formation of 3-substituted pyridines VIII. Presumably, the reaction occurs as follows. Dehydration of alcohol Ia–Id by the action of PPA gives alkenes IIa–IId which react with protonated 1,3,5-triazine (III) to form cationic species IVa–IVd. The latter undergo deprotonation to dihydrotriazines Va– Vd, opening of the triazine ring in Va–Vd leads to azapolyenes VIa–VId which are converted into dihydropyridines VIIa–VIId as a result of electrocyclic reaction or electrophilic addition. Finally, elimination of formamidine from compounds VIIa–VIId yields pyridines VIIIa–VIIId.

Reactions of 1,3-Dialkyl-5-amino-1,3-dihydro-2H-imidazo-[4,5-b]pyridin-2-ones with acetylacetone and ethyl acetoacetate

1,3-Dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones reacted with acetylacetone to give the corresponding 4-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)pent-3-en-2-ones which underwent intramolecular cyclization to 1,3-dialkyl-5,7-dimethyl-1,3-dihydro-2H-imidazo[4,5-b]-[1,8]naphthyridin-2-ones on heating in polyphosphoric acid or diphenyl ether. Analogous reaction of 1,3-dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones with ethyl acetoacetate led to the formation of ethyl 3-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)but-2-enoates whose cyclization afforded 1,3-dialkyl-8-hydroxy-7-methyl-1,3-dihydro-2H-imidazo[5,4-b][1,8]naphthyridin-2-ones.

Original Recyclization of S‐Phenacyl Derivatives of 4‐Acylamino‐2‐mercapto‐1,3‐oxazoles and Their Analogues.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Original recyclization of S‐phenacyl derivatives of 4‐acylamino‐2‐mercapto‐1,3‐oxazoles and their analogues

AbstractReadily accessible acylamino(chloro)acetophenones, if treated with sodium rhodanide and α‐halogenocarbonyl compounds, provide 4‐acylamino‐5‐aryl‐2‐mercapto‐1,3‐oxazole derivatives which undergo recyclization on heating in polyphosphoric acid to give substituted 1,3‐thiazol‐2(3H)‐ones or 1,3‐thiazolidin‐2,4‐diones containing 2‐alkyl(aryl)‐5‐aryl‐1,3‐oxazol‐4‐yl residues at the N3 atom. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:432–437, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20317

Structure of the Product of the Beckmann Rearrangement, 2-Methyl-4,5,6,7-Tetrahydrobenzothiazol-7-one Oxime

Buu-Hoi et al. [2] described the Beckmann rearrangement of oxime III, occurring on heating in polyphosphoric acid (PPA), and identified the product as 2-methyl-4,5-dihydro-8H-thiazolo[5,4-b]azepin-7(6H)one IV. We performed the Beckmann rearrangement of oxime III under the same conditions but obtained a product whose physicochemical properties fully coincide with those of compound II obtained by the Schmidt reaction. Thus, the Beckmann rearrangement of oxime III yields thiazoloazepine II and not IV. The H NMR spectra were taken on a Bruker WM250 spectrometer (250 MHz, internal reference TMS). The mass spectra were taken with an MKh-1321 mass spectrometer using the direct inlet system (ionizing electron energy 70 eV).

Stereoselectivity of cyclisations via N-acyliminium ions to form pyrido[2′,3′:3,4]pyrrolo[2,1-a]isoindole, -isoquinoline and -benz[c]azepine ring systems

Pyrido[2′,3′:3,4]pyrrolo[2,1-a]isoindole, -isoquinoline and -benz[c]azepine derivatives are obtained by heating in polyphosphoric acid (PPA) appropriate hydroxy lactam precursors derived from pyridine-2,3-dicarboximides. The stereoselectivity of ring closure is rationalised by considering the development of A(1,3) strain in the cyclisation step from N-acyliminium ion intermediates.

Preparation of 1,2‐disubstituted‐3‐hydroxy‐4(1H)‐quinolinones and the influence of substitution on the course of cyclization

AbstractSynthesis of 1,2‐disubstituted‐3‐hydroxy‐4(1H)‐quinolinones by the cyclization of N‐substituted phenacyl or acetonyl anthranilates is described. Two methods were employed for cyclization of anthranilates. Heating in polyphosphoric acid has a wide scope of applicability. The thermal cyclization in boiling N‐methylpyrrolidone is limited by steric effect.

ChemInform Abstract: Cyclization of Phenacyl 2‐{[2,2‐Di(ethoxycarbonyl)vinyl]amino}benzoate.

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General synthetic route to benz[g]isoquinolines (2‐azaanthracenes)

AbstractBenzylic zinc reagents add with high regioselectivity to 1‐(phenoxycarbonyl) salts derived from pyridine‐3‐carboxaldehyde (1a) or 3‐acetylpyridine (1b) to yield 1‐(phenoxylcarbonyl)‐4‐benzyl‐1,4‐dihydropyridine‐3‐carboxaldehydes 5a, 5c or ketones 5b, 5d. Aromatizations of these dihydro analogues with sulfur led to the corresponding aldehydes 6a, 6c or ketones 6b, 6d. An alternate synthesis to the aldehydic precursors involved additions of benzylic zinc reagents to 1‐(phenoxycarbonyl) salts formed from methyl nicotinates which led to the corresponding methyl 1‐(phenoxycarbonyl)‐4‐benzyl‐1,4‐dihydronicotinates 7a, 7b. Aromatizations of 7a, 7b led to the corresponding pyridine esters 8a, 8b which on reduction with lithium aluminum hydride yielded the corresponding carbinols 9a, 9b. Oxidation of 9a, 9b by manganese dioxide afforded aldehydes 6e, 6f. Aldehydes 6a‐f were readily converted into the benz[g]isoquinolines 10a‐f on heating in polyphosphoric acid.

Cyclization of Phenacyl 2-{[2,2-Di(ethoxycarbonyl)vinyl]amino}benzoate

Reaction of phenacyl anthranilate (1) with diethyl (ethoxymethylidene)malonate afforded phenacyl 2-{[2,2-di(ethoxycarbonyl)vinyl]amino}benzoate (2) which on heating in polyphosphoric acid underwent degradation. Thermal cyclization of 2 in diphenyl ether gave phenacyl 3-(ethoxycarbonyl)-4-oxo-1,4-dihydroquinoline-8-carboxylate (4). The phenacyl group did not cyclize even on prolonged heating at 250 °C. Heating in sulfuric acid resulted in hydrolysis of the ethyl ester under formation of 4-oxo-8-[(phenacyloxy)carbonyl]-1,4-dihydroquinoline-3-carboxylic acid (6). The structure of 4 was confirmed by an independent synthesis.