Photocyclization reactions. Part 4 . Synthesis of naphtho[1,8-bc]-furans and cyclohepta[cd]benzofurans using photocyclization of Ethyl 2-(8-Oxo-5,6,7,8-tetrahydro-1-naphthyloxy)acetates and ethyl 2-(5-Oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-4-yloxy)acetates

Photocyclization reactions were carried out on ethyl 2-(8-oxo-5,6,7,8-tetrahydro-1-naphthyloxy)acetates 1a-e and ethyl 2-(5-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-4-yloxy)acetates 2a-e in acetonitrile. Irradiation of 1a-e gave naphtho[1,8-bc]furanols 3a-e and naphtho[1,8-bc]furans 4a-e in 33–83% yields and ethyl acrylates 5b-d were produced in 3–25% yields during irradiation of 1b-d . On the other hand, 2a-e afforded cyclohepta[ad|benzofuranols 6a-e and cyclohepta[ad]benzofurans 7a-e in 44–87% yields. Ethyl acrylates 8b-d were also produced in 7–43% yields from irradiation of 2b-d . Substituent effects on photocyclization and reaction pathways are discussed.     

Nitrogen bridgehead compounds. Part 50 . Vilsmeier-haack acylation of 6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones,Part 5

6-Methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones 1-5 were subjected to Vilsmeier-Haack acylation with complexes of phosphoryl chloride and different amides. Acylation at position 9 of the pyridopyrim-idines was successful with the iminium salt formed in situ from N-formylpiperidine, N-methylformanilide or N,N-diethylbenzamide, but unsuccessful with the iminium salt formed from N,N-diethylacetamide or N,N-di-ethylisobutyramide, respectively. The iminium salt formed from formanilide, N-methylpyrrolidinone or formamide reacted only with those tetrahydropyridopyrimidinones which contain a strongly electronegative substituent (e.g. CN or CO₂Et) in position 3. With the latter derivatives, the 9-phenylaminomethylene group could be introduced using N,N-diphenylformamide or in a “one-pot” procedure with aniline and triethyl orthoformate. Ethanolysis of 9-N-methyl-N-phenylaminomethylene derivatives 15 and 19 afforded 9-ethoxy-methylene compounds 26 and 27 in the presence of hydrogen chloride. The structures of the 9-substituted 6-methyltetrahydropyridopyrimidin-4-ones 14-25 were elucidated by means of uv, ¹H and ¹³C nmr spectroscopy. 9-Piperidinomethylene 14 , 9-(N-methyl-N-phenylaminomethylene 15-19 and 9-(N-methyl-2-pyrrolidinylidene) 21 derivatives exist as E geometric isomers. 9-Phenylaminomethylene-6-methyl-4-oxo-6,7,8,9-tetra-hydro-4H-pyrido[1,2-a]pyrimidine-3-carbonitrile 20 displays a solvent-dependent E-Z isomerism. The bis-compound 25 contains both E and Z geometric exo C ? CH double bonds. 9-Benzoyl derivatives 23 and 24 exist predominantly as the 1,6,7,8-tetrahydropyridopyrimidin-4-one tautomer.     

Synthesis of 1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-c]pyridin-5-ones. I. 3-unsubstituted compounds

Synthesis of 1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-c]pyridin-5-ones via a Pechmann condensation of 3-carbethoxy-1-methyl-4-piperidone with various phenols is described. The limitations of this method are discussed. Synthesis of the parent ring system 3a via reduction of 1,2,3,4-tetrahydro-3-(phenylmethyl)-8-[(1-phenyl-1H-tetrazol-5-yl)oxy]-5H-[1]benzopyrano[3,4-c]pyridin-5-one ( 5 ) is also described.     

Furan derivatives. Part 9. Synthesis and properties of cyclohepta[cd]benzofurans

Cyclohepta[cd]benzofurans 1a-c were synthesized by heating (5-oxo-5H-benzocyclohepten-4-yloxy)acetic acids 7a-c with sodium acetate in acetic anhydride or by irradiation of 7a-c in acetonitrile. Several reactions such as protonation, catalytic hydrogenation, Diels-Alder reaction, acylation, and photoreaction were examined for 1a-b . The results show that cyclohepta[cd]benzofurans have both properties of heptafulvene and benzofuran. The carbon-carbon double bond in the furan ring of 1a has aromatic character, however, the carbon-carbon double bonds in the seven-membered ring have olefinic character.     

Nitrogen bridgehead compounds. Part 77. Addition reaction of 9-methylene-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones

Addition of bromine or thioacetic acid onto 6-methyl-9-methylenetetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones is stereoselective and gives the cis 6-Me,9-CH substituted products. Addition is also stereoselective in respect to the C(9) and C(10) centers, and gives as the primary product the erythro diastereomer, which may then undergo epimerization to the threo isomer. Relative configuration and predominant conformation of the products were determined by 1D and 2D nmr methods.     

Photocyclization reactions. Part 5. Synthesis of dihydrobenzofuranols using photocyclization of 2-alkoxybenzophenones and ethyl 2-benzoylphenoxyacetates

Photocyclization reactions were carried out on 2-alkoxybenzophenones 1a-h and ethyl 2-benzoylphenoxyacetates 2a -e in acetonitrile. Irradiation of 1a-h gave dihydrobenzofuranols 4a-h in 68–84% yields. Similarly, irradiation of 2a-e afforded dihydrobenzofuranols 8a-e in 72–75% yields. Ethyl acrylates 9b-c were also produced in 6–8% yields from photoreactions of 2b-c . Substituent effects on cyclization of 1,5-biradical intermediates and reaction pathways are discussed. Benzophenones are useful compounds to prepare dihydrobenzofuranols by photocyclization.     

Photocyclization reactions. Part 2 Synthesis of dihydrobenzofuranols using photocyclization of ethyl 2-formylphenoxyacetates and ethyl 2-acetylphenoxyacetates

Photocyclization reactions were carried out on ethyl 2-formylphenoxyacetates 1a-e and ethyl 2-acetylphenoxyacetates 2a-e in acetonitrile. Irradiation of 1a-e gave dihydrobenzofuranols 3 in 20–46% yields. Similarly, irradiation of 2a-e afforded dihydrobenzofuranols 6 and their derivatives 7, 8 in 40–86% yields. Substituent effects on photocyclization and reaction pathways are discussed.     

Nitrogen bridgehead compounds. Part 45 [1]. Synthesis of 6-arylhydrazono-6,7,8,9-tetrahydro-11H-pyrido-[2,1-b]quinazolin-11-ones

A series of 6-arylhydrazono-6,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolin-11-ones 3–37 , conveneint starting materials for indolopyridoquinazolines, were prepared by diazonium coupling between aryldiazonium chlorides and 6,7,8,9-tetrahydro- 2 , 6-formyl-5,7,8,9-tetrahydro- 39 , 6-(dimethylamino)methylene-6,7,8,9- 38 or 6-carboxyl-5,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolin-11-ones 43 . The arylhydrazono derivatives were also prepared from 6-bromo- 45 or 6,6-dibromo-6,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolines 46 with arylhydrazines. The structures of the 6-arylhydrazonopyridoquinazolines were characterized by uv and ¹H nmr spectroscopy. The 6-arylhydrazono derivatives show a solvent-dependent E-Z isomerism.     

Synthesis of 4-aryl-4,7,8,9-tetrahydro-6H-pyrazolo[3,4-b]quinolin-5-ones

Reaction of 5-amino-3-methyl-1-phenylpyrazole ( 1a ) and 5-amino-3-(4-chlorophenyl)-1H-pyrazole ( 1b ) with dimedone ( 2 ) and p-susbstituted benzaldehydes 3 in ethanol, afforded in all cases tricyclic linear 4-aryl-7,7-dimethyl-4,7,8,9-tetrahydro-6H-pyrazolo[3,4-b]quinolin-5-ones ( 4a-j ) in good yields. The linear structures and hence the regiospecificity of the reaction were established by nmr measurements.     

Reaction of dichloroketene and sulfene with N,N-disubstituted 6-amino-methylene-b,7,8,9 -tetrahydro-5H-benzocyclohepten-5-ones. Synthesis of 6-(2,2-Dichloroethylidene)-b,7,8,9-tetrahydro-5H-benzocyclohepten-5-one and of 5H-benzo[3,4]cyclohepta[2,l-b]pyran and 5H-Benzo[3,4]cyclo-hepta[1,2-e]-1,2-oxathiin derivatives

The 1,4-cycloaddition of dichloroketene to N,N-disubstituted 6-aminomethylene-b,7,8,9-tetra-hydro-5H-benzocyclohepten-5-ones afforded N,N-disubstituted 4-amino-3,3-dichloro-3,4,6,7-tetrahydro-5H-benzo[3,4]cyclohepta[2,l-b]pyran-2-ones only in the case of aromatic or strong hindering aliphatic N-substitution. The adducts gave N,N-disubstituted 4-amino-3-chloro-b,7-dihydro-5H-benzo[3,4]cyclohepta[2,l-b]pyran-2-ones by dehydrochlorination with collidine. Upon chromatography on neutral alumina, two products were instead isolated in the case of usual aliphatic N-substitution (diethylamine, piperidine), namely 6-(2,2-dichloroethylidene)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-one and the dehydrochlorinated 2-pyrone; this latter was the sole product in the case of pyrrolidine substitution. The 1,4-cycloaddition of sulfene occurred readily to give N,N-disubstituted 4-amino-3,4,6,7-tetrahydro-5H-benzo[3,4]cyclohepta-[1,2-e]-1,2-oxathiin 2,2-dioxidesin the case of both aliphatic and partially aromatic N-substitution.     

Synthesis of some 5-Aryl-4,5-dihydro[1]benzoxepin-3(2H)-ones and 5-aryl-5,6,8,9-tetrahydro-7H-benzocyclohepten-7-ones from benzoxepinoisoxazolone and benzocycloheptaisoxazolone derivatives

Some 5-aryl-4,5-dihydro[1]benzoxepin-3(2H)-ones and 5-aryl-5,6,8,9-tetrahydro-7H-benzocyclohepten-7-ones were synthesized by hydrogenolytic cleavage of the isoxazole ring of 4-aryl-3-oxo-3,3a,4,10-tetrahydro[1]-benzoxepino[3,4-c]isoxazoles or 4-aryl-3-oxo-3a,4,9,10-tetrahydro-3H-benzo[4,5]cyclohepta[1,2-c]isoxazoles which in turn were prepared from ethyl 3-oxo-4-phenoxybutanoate or ethyl 3-oxo-5-phenylpentanoate by simple methods.     

Furan derivatives. Part 8 On substituent effects in the synthesis of 4,5-dihydro-3H-naphtho[1,8-bc]furans

4,5-Dihydro-3H-naphtho[1,8-bc]furans 4 and 6 which have various substituents (R¹ and R²) have been synthesized from 8-oxo-5,6,7,8-tetrahydro-1-naphthyloxyacetic acids 1 and 3 or their ethyl esters 2 . The reaction of acids 1 and 3 with sodium acetate in acetic anhydride gave a mixture of furans 4 and 6 and lactones 5 and 7 . The ratios of the products were varied according to the types of substituents (R¹ and R²) in acids 1 and 3 . As the substituent R¹ (R² = hydrogen) in acids 1 was changed from hydrogen to a methyl, ethyl or isopropyl group, production of furans 4 became more difficult. However, when a phenyl group was used as the substituent, furan 4 was obtained in good yield. Similarly, as the substituent R² (R¹ = hydrogen) in acids 1 was changed from hydrogen to a methyl, ethyl or isopropyl group, furan formation was more difficult. In contrast, acids 3 which had electron-withdrawing substituents such as chlorine, bromine or a nitro group at the 4-position afforded furans 6 in good yield. 4,5-Dihydro-3H-naphtho[1,8-bc]furans 4 and 4,5-dihydro-3H-naphtho[1,8-bc]furan-2-carbocylic acids 8 were synthesized from the reaction of esters 2 and potassium hydroxide in dioxane. When the substituents R¹ or R² in esters 2 were varied from hydrogen to a methyl, ethyl or isopropyl group the total yields of furans 4 and furancarboxylic acids 8 were reduced.     

Synthesis of 2-Aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones and 7-Aryl-2,3,6,7-tetrahydro-5H-imidazo[2,1-b]-1,3-thiazin-5-ones

The reaction of 2-mercaptobenzimidazole, 5-ethoxy-2-mercaptobenzimidazole, and 2-mercaptoimidazoline with cinnamoyl chloride, its derivatives, and heteroanalogs was studied. Convenient methods were found for the synthesis of 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones and 7-aryl-2,3,6,7-tetrahydro-5H-imidazo[2,1-b]-1,3-thiazin-5-ones.     

Synthesis and spectra of 7-(o- and p-R-phenyl)-10,10-dimethyl-8,9,10,11-tetrahydrobenz[c]acridin-8-ones. Structure correction of 1,2,3,4-tetrahydro-2,2-dimethyl-5-aryl-6-aza-7,8-benzophenanthren-4-ones

It has been reported that dimedone added to α-arylidennaphthylamines in ethanol with formation of 1,4-addition products derivatives of 5-aryl-5,6,7,8,9,10-hexahydrobenzo[c]phenanthridin-7-ones, III , which are easily oxidized by chromic anhydride to the corresponding tetrahydro derivatives, IV . However, the attempted preparation of these compounds resulted instead of the formation of isomeric acridin-8-ones V and VI . Structures were confirmed by ir, ¹ H nmr, ms and X-ray spectroscopy.     

Psilocin analogs. III. Synthesis of 5-methoxy- and 5-hydroxy-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indoles

A number of tetrahydro-β-carbolines were prepared with oxygen substituents at C-5. This class of compounds represents a hybrid between two naturally occurring groups of hallucinogenic molecules, the 4-hydroxytryptamines and the 6- and 7-oxygenated β-carbolines.     

Synthesis of trans 8-substituted-6-phenyl-6,7,8,9-tetrahydro-3H-pyrazolo [4,3-f]isoquinolines using a Pictet-Spengler approach

In the following communication we report two complementary approaches for the synthesis of trans 8-substituted-6-phenyl-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolines. The first method, directly from α-methyl substituted indazole ethanamines, was successful but had limited substrate scope. The second method utilised a modified Pictet-Spengler cyclisation reaction on an aniline substrate followed by late stage construction of the indazole ring and was more versatile in terms of substrate scope.     

Synthesis of 5-amino-4,5-dihydropyrazolo [3,4-d] pyrimidin-4-ones and related isomeric systems : Part II. Ring closure reactions

Treatment of ethyl (heteroalkylidene)aminopyrazole-4-carboxylates with hydrazine hydrate generally provides a ready synthetic route to 5-amino-4, 5-dihydropyrazolo [3,4-d] pyrimidin-4-ones, although ethyl 5-[(dimethylamino) alkylidene]aminopyrazole-4-carboxylates are unreactive.On the other hand, reactions between aminopyrazole-4-carboxhydrazides and orthoesters or amide acetal are more versatile : we observed formation of isomeric 2-pyrazolyl-1,3,4-oxadiazoles, as major compounds, either from triethyl orthoacetate and 1-methyl-5-aminopyrazole-4-carboxhydrazide or from dimethylacetamide dimethyl acetal and various heterocyclic precursors. The ring closure mechanism is discussed.     

Fused v-triazolo-heterocycles. Part 2. Synthesis of 4H-v-triazolo[1,5-d] [1,3,4]oxadiazin-4-ones from the 1-aroylamino-v-triazole-5-carboxylic acids

The synthesis of some 4H-v-triazolo[1,5-d] [1,3,4]oxadiazin-4-ones is described. They are prepared by the reaction of the corresponding 1-aroylamino-v-triazole-5-carboxylic acids with thionyl chloride in the presence of pyridine. The spectroscopic data of these new compounds are also reported.     

Chemical reactions of 5-alkyl-1,4-diaza- and 5-alkyl-1-aza-4-oxabicyclo[3.3.0]octan-8-ones

The behavior of 5-alkyl-1,4-diaza and 5-alkyl-1-aza-4-oxabicyclo[3.3.0]octan-8-ones has been studied towards catalytic reduction, reduction by lithium aluminum hydride, acylation, cyanoethylation, alkylation, etc. The oxazolidine ring in 5-alkyl-1-aza-4-oxabicyclo[3.3.0]octan-8-ones was readily opened by electrophilic and nucleophilic reagents whereas most of the reactions of 5-alkyl-1,4-diazabi-cyclo[3.3.0]octan-8-ones occurred with retention of the bicyclic structure.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 193–197, February, 1988.