1,4-Cycloaddition reactions. II. Preparation of p-dioxino[2,3-g]furo[3,2-c] quinolines,p-dioxino[2,3-f] furo[3,2-c] quinolines,and [1,3] dioxolo[4,5-g] furo[3,2-c] quinolines from 2,3-dihydro-5-methylfuran and schiff bases

The boron trifluoride catalyzed 1,4-addition of 2,3-dihydro-5-methylfuran to N-(p-methoxy-benzylidene)-1,4-benzodioxan-6-amine (II) gave 2 pairs of epimers, 2,3,3a,4,5,8,9,11b-octahydro-4-(p-methoxyphenyl)-11b-methyl-p-dioxino[2,3-g]furo[3,2-c]quinoline (IIIa and b) and 2,3,7,8,8a,9.10,1la-octahydro-8-(p-methoxyphenyl)-11a-methyl-p-dioxino[2,3-f]furo[3,2-c]quinoline (IVa and b). When N-(p-methoxybenzylidene)-3,4-methylenedioxyaniline (V) was condensed with 2,3-dihydro-5-methylfuran in an analogous manner, a mixture of 2 epimers of 2,3,3a,4,5,10b-hexahydro-4-(p-methoxyphenyl)-10b-methyl[1,3]dioxolo[4,5-g]furo[3,2-c]quinoline (VIa and b) was isolated. Treatment of this mixture with sulfur afforded 6-(p-methoxyphenyl)-8-methyl-1,3-dioxolo[4,5-g]quinoline-7-ethanol (VIII). Structural assignments for all of the products were made from NMR spectra. None of the compounds possessed appreciable biological activity.     

1,4-Cycloaddition reactions. III. Synthesis of furo[3,2-c]pyrido[2,3-g]quinolines,Furo[2,3-a] [4,7]phenanthrolines,Furo[3,2-c]pyrrolo[2,3-g]quinolines,Furo[3,2-c]pyrrolo[3,2-g]quinolines,and Furo[3,2-c]furo[2′,3′:4,5]pyrido[2,3-g]quinolines from 2,3-dihydro-5-methylfuran and schiff bases

The 1,4-cycloaddition of 2,3-dihydro-5-methylfuran (II) to 1-acetyl-1,2,3,4-te trahydro-6-[(p-hydroxybenzylidene)amino]quinoline (VIII) in the presence of boron trifluoride gave two pairs of epimers, namely dl-10-acetyl-2,3,3a,4,5,7,8,9,10,11b-decahydro-4-(p-hydroxyphenyl)-11b-methylfuro[3,2-c]pyrido[2,3-g]quinoline (IXa and b) and dl-8-acetyl-2,3,3a,4,5,8,9,10,11,-11c-decahydro-4-(p-hydroxyphenyl)-11c-methylfuro[2,3-a][4,7]phenanthroline (Xa and b). dl-9-Acetyl-3,3a,4,5,7,8,9,10b-octahydro-4-(p-hydroxyphenyl)-10b-methyl-2H-furo[3,2-c] pyrrolo-[2,3-g]quinoline (XIIIa) was the predominant product isolated from the reaction of II with 1-acetyl-5-[p-(hydroxybenzylidene)amino]indoline (XII). When 1-acetyl-6-[(p-hydroxybenzylidene)amino]indoline (XVI) was treated with 2,3-dihydro-5-methylfuran (II), two epimers of dl-7-acetyl-3,3a,4,5,7,8,9,10b-octahydro-4-(p-hydroxyphenyl)-10b-methyl-2H-furo[3,2-c]pyrrolo[3,2-g]quinoline (XVIIa and b) were obtained. dl-2,3,3a,4,5,6b,8,9,9a,10,11,12b-Dodecahydro-4,10-bis(p-methoxyphenyl)-6b,12b-dimethylfuro[3,2-c]furo[2′,3′:4,5]pyrido[2,3-g]quinoline (XX) was formed when 2,3-dihydro-5-methylfuran was allowed to react with N,N'-bis(p-methoxybenzylidene)-p-phenylcnediamine (XIX). Structure assignments were made from NMR spectra. None of the compounds exhibited appreciable biological activity.     

Furopyridines. II. Bromination and nitration of furo[2,3-b]-, furo[3,2-b]-, furo[2,3-c]- and furo[3,2-c]pyridine

In order to reveal the reactivities of furopyridines, we undertook bromination and nitration of four furopyridines ( 1, 2, 3 and 4 ) whose chemical properties had been almost unknown. Bromination of 1, 2, 3 and 4 gave the corresponding trans-2,3-dibromo-2,3-dihydro derivatives 6, 8, 10 and 12 , respectively, which were converted to 3-bromofuropyridines 7, 9, 11 and 13 by treatment with sodium hydroxide in aqueous methanol. Nitration of 1 with a mixture of fuming nitric acid and sulfuric acid afforded a mixture of addition products 14a, 14b and 14c and 2-nitro derivative 15 . Both 14a and 14b were easily converted to 15 by treatment with sodium bicarbonate. Compound 2 was nitrated to give a mixture of cis- and trans-2-nitro-3-hydroxy-2,3-dihydro derivative 16a and 16b and 2-nitro derivative 17 . The cis isomer 16a was transformed to the trans isomer 16b by refluxing on silica gel in ethyl acetate. Compound 16b was dehydrated with acetic anhydride to give 17 . Nitration of 3 gave a nitrolic acid derivative 20 . Nitration of 4 gave a mixture of 2-nitro derivative 22 and 3-(trinitromethyl)pyridin-4-ol ( 23 ). The structures of 20 and 23 were established by single crystal X-ray analysis. The differences of behavior observed in these reactions are discussed in connection with the results of the determination of pKa values and the relative reactivities of deuteriodeprotonation of these furopyridines.     

Furopyridines. XIV. Synthesis of 2-aminoalkyl derivatives of furo[2,3-b]-, furo[3,2-b], furo[2,3-c]- and furo[3,2-c]pyridine

The preparation of 2-aminomethyl- 3a-d , 2-acetamidomethyl- 4a-d , 2-N,N-dimethylaminomethyl- 5a-d , 2-(1-hydroxy-2-nitroethyl)- 6a-d , 2-(1-hydroxyl-2-aminoethyl)- 7a-d and 2-(1-hydroxy-2-N,N-dimethylaminoethyl)- 8b-d derivatives of furo[2,3-b]-, furo[3,2-b]-, furo[2,3-c]- and furo[3,2-c]pyridine is described.     

Furopyridines. IX. Syntheses and properties of 3-ethoxy derivatives of furo[2,3-b]-, furo[3,2-b]-, furo[2,3-c]- and furo[3,2-c]pyridine

Reaction of ethyl 3-ethoxycarbonylmethoxyfuropyridine-2-carboxylates 2a-2d with sodium ethoxide afforded 3-ethoxy derivatives 3a-3d which converted to 3-ethoxyfuropyridines 5a-5d by hydrolysis and decarboxylation of the ester group. Vilsmeier reaction of 5a and 5b gave 2-formyl-3-ethoxy derivatives 6a and 6b and 2-formyl-3-chloro derivatives 7a and 7b , while 5c and 5d did not give any formyl compound. Bromination of 3-ethoxyfuropyridines with 1 equivalent mole of bromine gave 2-bromo-3-ethoxyfuropyridines 9a-9d , whereas reaction with 3 equivalents of bromine yielded 2,2-dibromo-3,3-diethoxy-2,3-dihydrofuropyridines ( 10a and 10b ) and/or 2-bromo-3,3-diethoxy-2,3-dihydrofuropyridines 11b , 11c and 11d . Treatment of compounds 5a-5d with n-butyllithium in hexane-tetrahydrofuran at ?70° and subsequent addition of N,N-dimethylformamide yielded 2-formyl derivatives 6a-6d .     

Furopyridines. XXIII. Synthesis and reactions of chloropyridine derivatives of furo[2,3-b]-, -[2,3-c]- and -[3,2-c]pyridine

Chlorination of the N-oxides of furo[2,3-b]- 1a , -[2,3-c]- 1b and -[3,2-c]pyridine 1c with phosphorus oxychloride afforded compounds substituted normally at the α- or λ-position to the ring nitrogen, 2a, 2′a, 2b, 2c, 2′c and 2′c , and in addition, in the case of 1b , compounds substituted on the furan ring, 2′b and 2″b . The structures of these compounds were confirmed from their ir, nmr and mass spectra. The major chlorinated products 2a, 2b and 2c were converted to methoxy- 5a, 5b and 5c , N-pyrrolidyl- 7a, 7b and 7c , and phenylthiofuropyridines 8a, 8b , and 8c .     

Furopyridines. VII. Preparation and hydrolysis of 2-cyano and 3-cyano derivatives of furo[3,2-b]-, furo[2,3-c]- and furo[3,2-c]pyridine

This paper describes the preparation and hydrolysis of 2-cyano and 3-cyano derivatives of furo[3,2-b]-, furo[2,3-c]- and furo[3,2-c]pyridine. Treatment of furopyridines 1a , 1b and 1c with n-butyllithium in hexane-tetrahydrofuran at -70° and subsequent addition of N,N-dimethylformamide yielded 2-formyl derivatives 2a , 2b and 2c. Dehydration of the oximes 4a , 4b and 4c of 2a , 2b and 2c gave 2-cyano compounds 5a , 5b and 5c , which were hydrolyzed to give 2-carboxylic acids, 6a, 6b and 6c , respectively. Reaction of 3-bromo compounds 7a , 7b and 7c with copper(I) cyanide in N,N-dimethylformamide afforded 3-cyano derivatives 8a , 8b and 8c. Alkaline hydrolysis of 8a , 8b and 8c gave compounds formed by fission of the 1-2 bond of furopyridines 9a , 9b and 9c , while acidic hydrolysis gave the corresponding carboxamides, 10a , 10b and 10c.     

Furopyridines. X. Synthesis of tricyclic heterocycles,furo[2,3-b:4,5-c']-, furo[3,2-b:4,5-c']-, furo[2,3-c:4,5-c']- and furo[3,2-c:4,5-c']dipyridine

This paper describes the synthesis of four tricyclic heterocycles, furo[2,3–6:4,5-c']- ( 5a ), furo[3,2-b:4,5-c']- ( 5b ), furo[2,3-c:4,5-c']- ( 5c ) and furo[3,2-c:4,5-c']dipyridine ( 5d ). Starting with 2-formylfuropyridines ( 1a-d ), β-(2-furopyridyl)acrylic acids 2a-d were obtained by condensing with malonic acid. The acrylic acids were converted to the acid azides by reaction with ethyl chloroformate and the subsequent reaction with sodium azide. Heating of the acid azides at 230–240° with diphenylmethane and tributylamine gave tricyclic pyridinones 3a-d , which were converted to the respective chloro derivatives 4a-d by reaction with phosphorus oxychloride. Reduction of the chloro compounds over palladium-charcoal yielded compounds 5a-d respectively. All the compounds 2 to 5 were characterized by elemental analysis and spectral data. The H and ¹³C nmr and electronic spectral features of the furodipyridines were discussed comparing with those of the parent furopyridines.     

Furopyridines. XII . Reaction of 3-bromo, 2-phenylthio and 2-phenylthio-3-bromo derivatives of furo[2,3-b]-, furo[3,2-b]-, furo[2,3-c]- and furo[3,2-c]pyridine with several alkyllithiums

This paper describes reactions of 3-bromo- 1a-d , 2-phenylthio- 5a-d and 2-phenylthio-3-bromofuropyridines 6a-d with n-butyl-, t-butyl- and methyllithium and lithioacetonitrile. Lithiation of compounds 1a-d with n-butyl- or methyllithium gave the parent furopyridines 2a-d and o-ethynylpyridinols 3a-d. Reaction of compounds 5a-d with methyllithium afforded o-(phenylthioethynyl)pyridinols 7a-d , which were also yielded by reaction of compounds 6a-d with t-butyl- or methyllithium. The phenylthio group in compounds 7a-d were substituted with t-butyl group by the reaction with excess t-butyllithium. In contrast, 2-phenylthio group in compounds 5a-d and 6a-d was substituted with cyanomethyl group by reaction with lithioacetonitrile to give compounds 11a-d and 10b, c respectively.     

Furopyridines. XIX. Reaction of furo[2,3-b]-, -[3,2-b]-, -[2,3-c]- and -[3,2-c]pyridine with acetic anhydride

Acetoxylation of N-oxide of furo[2,3-b]- 2a , -[3,2-b]- 2b , -[2,3-c]- 2c and -[3,2-c]pyridine 2d with acetic anhydride afforded compounds substituted normally at the α- or γ-position to the ring nitrogen, 3a, 4a, 4b, 3d, 4d, 8 and 9 , and in addition compounds substituted on the furan ring, 5a, 6a, 5b, 6b, 7b, 5c and 7c which were unexpected compounds. The structures of these compounds were established from the ir, nmr and mass spectra, and x-ray crystal analysis of 5b .     

N-Arylindne 1,4-Cycloaddition Reaction.Preparation of Substituted Hexahydrofurol[3,2-c]quinolines

Thesynthesisofnitrogenheterocyclesthroughcycloadditionreactionofimineshasstimulatedmuchpreparativeandmechanistic.ork'.ThereactionofShiffbaseswithelectron~richolefinshasbeenutilizedfOrthesysthesisofquinolinederi.ati.es2'3.WehavestudiedthecycloadditionofN-arylideneanilineIwith2,3-dihydrofuranandobtainedagroupofsubstitutedhexahydrofuro[3,2-c]quinolines.Generally,thereactionofbenzaldehydewithanilinegiveseasilythecorrespondingN-benzilideneaniline'.Butbenzaldehydewithanelectron-donatinggroupandani…     

Condensed pyridine bases. Electrophilic substitution in 1,7-dimethyl-3(2H)-benzo[b]furo[2,3-c]pyridone

Nitration, bromination, thiocyanation, and acylation of 1, 7-dimethyl-3(2H)-benzo[b]furo[2, 3-c]pyridone were investigated. It was shown that either the 4-nitro- or the 4,6-dinitro derivative is formed as a function of the nitration conditions. Bromination with bromine and thiocyanation with dithiocyanogen yields a bromo derivative at position 4. The product of substitution at the C₍₆₎, atom is obtained in acylation with acetyl chloride, and the product of substitution at atoms C₍₄₎ and C₍₆₎ is obtained with benzoyl chloride. The results of the calculations were generalized in the MNDO approximation.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 534–541, April, 1996     

Synthesis of Benzo[d]Benzo[2,3][1,4]Diazepino[1,7-b]Isothiazole,a New Heterocyclic Ring System

A facile synthesis of benzo[d]benzo[2,3][1,4]diazepino[1,7-b] isothiazole, a new heterocyclic ring system is reported.     

Furopyridines. XXII. Elaboration of the C-substituents alpha to the heteronitrogen atom of furo[2,3-b] -, -[3,2-b] -, -[2,3-c]- and -[3,2-c]pyridine

The Grignard reaction of fused ring cyanopyridine derivatives 1a-d with methyl- and phenylmagnesium bromide yielded the corresponding acylpyridine compounds 2a-d and 3a-d . Furopyridine N-oxides 4a-d were converted into the compounds having a phenyl group at the α-position to the ring nitrogen 5a-d . Reduction of 1a-d and the carboxylic esters 6a-d with diisobutylaluminium hydride yielded the corresponding amines 7a-d and aldehydes 9a-d . The aldehydes were converted to nitroethanol derivatives 10a-d by condensation with nitromethane and acrylic ester compounds 11a-d by the Wittig-Horner reaction with methyl diethyl phosphonoacetate.     

Furopyridines. XXVIII. Reactions of 3-bromo derivatives of furo[2,3-b]-, -[3,2-b]-, -[2,3-c]- and -[3,2-c]pyridine and their N-oxides

Bromination of 3-bromofuro[2,3-b]- 1a , -[3,2-b]- 1b and - [3,2-c]pyridine 1d afforded the 2,3-dibromo derivatives 2a, 2b and 2d , while the -[2,3-c]- compound 1c did not give the dibromo derivative. Nitration of 1a-d gave the 2-nitro-3-bromo compounds 3a-d . The N-oxides 4a-d of 1a-d were submitted to the cyanation with trimethylsilyl cyanide to yield the corresponding α-cyanopyridine compound 6a-d . Chlorination of 4a and 4d with phosphorus oxychloride gave mainly the chloropyridine derivatives 7a, 7′a and 7d , while 4b and 4c gave mainly the chlorofuran derivatives 7′b and 7′c accompanying formation of the chloropyridine derivatives 7b, 7′b and 7c . Acetoxylation of 4a and 4b with acetic anhydride yielded the acetoxypyridine compounds 8a, 8′a and 8b , while 4c and 4d gave the acetoxypyridine 8′c, 8′d and 8′d , pyridone 8c and 8d , acetoxyfuran 8′c and dibromo compound 9c and 9′c.     

Condensed pyridine bases synthesis of some benzo[b]furo[2,3-c]-, benzo[b]- thieno[2,3-c]-, and benzo[b]selenopheno[2,3-c]-quinolines

Summary Condensation of benzo[b]furan-3(2H-one, benzo[b]thiophen-3(2H)-one and benzo[b]selenophen-3(2H)-one with dimedone gives 2-(3-heteryl)dimedones. Acylation of the latter leads to the corresponding tetracyclic pyrylium salts, from which condensed quinolines are obtained. Some condensed quinoline derivatives are obtained by reaction of 1-oxo-1,2,3,4-tetrahydroheterene[2,3-c]quinolines with sodium borohydride, hydrazine, and hydroxylamine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 321–326, March, 1994.     

Furopyridines. XXVII. Reactions of 2-methyl and 2-cyano derivatives of furo[2,3-b]-, -[3,2-b]-, - [2,3-c]- and -[3,2-c]pyridine

Bromination of 2-methylfuropyridines 1a-d-Me gave the 3-bromo derivatives 2a-d , while the 2-cyano compounds 1a-d-CN resulted in the recovery of the starting compounds. Nitration of 1a-d-Me and 1a-d-CN did not yield the corresponding nitro derivative, except for 1-c-CN giving 3-nitro derivative 3c in 7% yield. N-Oxidation of 1a-d-Me and 1b-d-CN with m-chloroperbenzoic acid yielded the N-oxides 4a-d-Me and 4b-d-CN , whereas 1a-CN did not afford the N-oxide. Cyanation of N-oxides 4a-d-Me and 4b-d-CN with trimethylsilyl cyanide gave the corresponding α-cyanopyridine compounds 5a-d-Me and 5b-d-CN . Chlorination of 4a-d-Me and 4b-d-CN with phosphorus oxychloride also gave the α-chloropyridine compounds 6b-d-Me and 6b-d-CN , accompanying formation of γ-chloropyridine 6a-Me, 6′b-Me and 6′b-CN , β-chloropyridine 6′b-CN , and α'-chloropyridine derivatives 6′c-Me and 6′c-CN . Acetoxylation of 4a-d-Me and 4b-d-CN with acetic anhydride yielded α-acetoxypyridine compounds 7a-Me and 7b-CN , pyridone compounds 11d-Me, 11c-CN and 11d-CN , 3-acetoxy compounds 8, 9b, 9c , and 2-acetoxymethyl derivatives 10b and 10c.     

Synthesis and cycloaddition reactions of ethyl glyoxylate imines. Synthesis of substituted furo-[3,2-c]quinolines and 7H-indeno[2,1-c]quinolines

Lewis acid catalyzed cycloaddition reactions of ethyl glyoxylate imines to dihydrofuran and indene yield substituted hexahydrofuro[3,2-c]- and tetrahydro-7H-indeno[2,1-c]quinolines respectively. Oxidation of the adducts with 2,3-dichloro-5,6-dicyanobenzoquinone affords the corresponding aromatic compounds.     

Furopyridines. XX. Wittig-horner reaction of a phosphonate of reissert analogues of furo[3,2-c]-, -[2,3-c]- and -[3,2-b]pyridines

Furo[3,2-c]-( 1a ), -[2,3-c]- ( 1b ) and -[3,2-b]pyridine ( 1c ) were reacted with isopropyl chloroformate and trimethyl phosphite to give dimethyl 5-isopropoxycarbonyl-4,5-dihydrofuro[3,2-c]pyridine-4-phosphonate ( 2a ), dimethyl 6-isopropoxycarbonyl-6,7-dihydrofuro[2,3-c]pyridine-7-phosphonate ( 2b ) and dimethyl 4-isopropoxycarbonyl-4,7-dihydrofuro[3,2-b]pyridine-7-phosphonate ( 2c ) as unstable syrups. Reaction of 2b and 2c with n-butyllithium and then with benzaldehyde, p-methoxybenzaldehyde, p-cyanobenzalde-hyde or propionaldehyde afforded the normal Wittig reaction products 5b-H, 5b-OMe, 5b-CN, 5b-Et, 5c-H, 5c-H, 5c-OMe and 5c-CN , except for 2b with propionaldehyde. While, the same reactions of compound 2a and the reaction of 2b with propionaldehyde afforded the unexpected products, 5-isopropoxycar-bonylfuro[3,2-c]pyridinio-4-aryl-(or ethyl)methoxides 3a-H, 3a-OMe, 3a-CN and 3a-Et , 4-(1′-aryl(or ethyl)-1′-hydroxymethyl)furo[3,2-c]pyridines 4a-H, 4a-OMe, 4a-CN and 4a-Et accompanying formation of the normal products. Treatment of the normal Wittig reaction products with lithium diisopropylamide and then with acetone gave the derivatives alkylated at the 2-or the benzylic positions.