The synthesis of benzofuroquinolines. V. Some benzofuro[3,2-B]quinoline derivatives

Some benzofuro[3,2-b]quinoline derivatives 1a-d and 3a were synthesized by condensation of 2-amino-benzaldehyde, 2-aminoacetophenone, 2-aminobenzophenone, isatin, or 2-aminobenzoic acid with 3(2H)-benzofuranone. The benzofuroquinolinone 3a was also obtained from 2-aminobenzoic acid and phenoxy-acetyl chloride in two steps and converted to 10-chloro derivative 1e . Similarly, some 8-halobenzofuro[3,2-b]-quinoline derivatives 1d,e and 3a (X = F, Cl, Br, I) were synthesized from 5-haloisatin or 2-amino-5-halo-benzoic acid. And benzofuro[3,2-b]quinolines 1a-e thus obtained were converted to corresponding N-oxides 2 .     

The synthesis of benzofuroquinolines. X. Some benzofuro[3,2-c]isoquinoline derivatives

Condensation of salicylonitrile with ethyl α-bromo-α-(o-ethoxycarbonylphenyl)acetate (4) effectively gave 5 (6H)-benzofuro[3,2-c]isoquinolinone (2) , which was converted to some 5-substituted benzofuro-[3,2-c]isoquinoline derivatives 1a-g.     

The synthesis of benzofuroquinolines. IV. Some halobenzofuro[2,3-B]- and [3,2-C]quinoline derivatives

Some 8- or 9-halobenzofuro[2,3-b]quinolines ( 1a , 8-F, 8-C1, 9-F, 9-Cl) and 9-halobenzofuro[2,3-b]quinoline-11-carboxylic acid ( 1b , F, Cl) were synthesized from 6- or 7-halo-3-(2-methoxyphenyl)-2-oxo-1,2-dihydroquino-line-4-carboxylic acids ( 3 ). And, some 9-halo-11(6H)-benzofuro[2,3-b]quinolinone ( 8 , F, Cl, Br) and 2-halo-6(5H)-benzofuro[3,2-c]quinolinone ( 9 , F, Cl, Br) were synthesized from 6-halo-4-hydroxy-3-(2-methoxyphenyl)-2(1H)-quinolinone ( 7 ), and they were converted to the corresponding chlorohalobenzofuroquinolines ( 1c , 9-F, 9-C1, 9-Br, and 2 , F, Cl, Br).     

A new synthesis of 2,3-dihydrofuro[2,3-b], [2,3-c] and [3,2-c]quinolines

A new synthesis of three isomeric dihydrofuroquinolines is described. This route via ortholithiation of O-quinolyl carbamates is considerably more effective than that which proceeds via lithiation of alkoxyquinolines.     

A concise synthesis of functionalized 2,3-dihydrofuro[3,2-b], [3,2-c], and [2,3-b]pyridines

A strategy for the efficient and rapid one-pot synthesis of 2-aryl-2,3-dihydrofuro[3,2-b], [3,2-c], and [2,3-b]pyridines from readily available o-nitropicolines and aromatic aldehydes is described. The key transformation involves reaction of o-nitropicolines with aromatic aldehydes in the presence of TBAF and Hünig's base giving rise to functionalized products having molecular complexity suitable for further manipulation.     

A new synthesis of benzofuro[3,2-c]pyridines

The condensation of O-phenylhydroxylamine with piperidin-4-one and 3-methylpiperidin-4-one has given 1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine and 4-methyl-1,2,3,4-tetrahydro-benzofuro [3,2-c]pyridine, and these have been dehydrogenated to the corresponding heteroaromatic system of benzofuro[3,2-c]pyridine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No.7, pp. 908–909, July, 1973.     

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. 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.     

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.     

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. 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. 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 .     

Furopyridines. XIII. Reaction of 2-methylfuro[2,3-b]-, -[3,2-b]-, -[2,3-c]- and -[3,2-c]pyridines with lithium diisopropylamide

Lithiation of 2-methylfuro[2,3-b]- 1a , -[2,3-c]- 1c and -[3,2-c]pyridine 1d with lithium diisopropylamide at ?75° and subsequent treatment with deuterium chloride in deuterium oxide afforded 2-monodeuteriomethyl compounds 2a, 2c and 2d , while 2-methylfuro[3,2-b]pyridine 1b gave a mixture of 1b, 2b , 2-methyl-3-deuteriofuro[3,2-b]pyridine 2′b and 2-(1-proynyl)pyridin-3-ol 5 . The same reaction of 1a at ?40° gave 3-(1,2-propadienyl)pyridin-2-ol 3 and 3-(2-propynyl)pyridin-2-ol 4 . Reaction of the lithio intermediates from 1a, 1c and 1d with benzaldehyde, propionaldehyde and acetone afforded the corresponding alcohol derivatives 6a, 6c, 6d, 7a, 7c, 7d, 8a, 8c and 8d in excellent yield; while the reaction of lithio intermediate from 1b gave the expected alcohols 6b and 8b in lower yields accompanied by formation of 3-alkylated compounds 9, 11, 12 and compound 5 . While reaction of the intermediates from 1a, 1b and 1d with N,N-dimethylacetamide yielded the 2-acetonyl compounds 13a, 13b and 13d in good yield, the same reaction of 1c did not give any acetylated product but recovery of the starting compound almost quantitatively.     

Furopyridines. XXIV. Nitration,chlorination, acetoxylation and cyanation of 2,3-dihydrofuro[2,3-b]-, -[3,2-b]-, -[2,3-c]- and -[3,2-c]pyridine N-Oxides

Nitration of 2,3-dihydrofuro[3,2-b]- N-oxide 3b and -[2,3-c]pyridine N-oxide 3c afforded the nitropyridine compounds 4b, 5b and 6 from 3b and 4c, 5c, 5′c and 7 from 3c , while -[2,3-b]- N-oxide 3a and -[3,2-c]pyridine N-oxide 3d did not give the nitro compound. Chlorination of 3b and 3c with phosphorus oxychloride yielded mainly the chloropyridine derivatives 15b, 15′b from 3b and 15c and 15′c from 3c , whereas 3a and 3d gave pyridine derivatives formed through fission of the 1–2 ether bond of the furo-pyridines 13a , 14 and 13d . Acetoxylation of 3b and 3c gave 3-acetoxy derivatives 18b and 18c and the parent compound 1b and 1c . Acetoxylation of 3a yielded compounds formed through fission of the 1–2 bond 16 and 17 and 3d gave furopyridones 19 and 19 ′. Cyanation of 3b and 3c yielded mainly the cyanopyridine compounds 20b, 20c and 20′c . Cyanation of 3a and 3d gave the cyanopyridine compounds 20a , 20d and 20′d accompanying formation of the pyridine derivatives 21a, 21d and 21′d .     

5H-Thiazolo [3,2-b]- and 2H-Thiazolo [2,3-c]-as-triazines

Derivatives of the 5H-thiazolo[3,2-b]- and 2H-thiazolo[2,3-c]-as-triazine systems were synthesized via condensation of tetrahydro-I-methyl-as-triazine-3(2H)-thione with ethylene dibromide and ethyl bromoacetate, respectively. An hypothesis is given for the formation of the [3,2-b] system in one of these reactions and the [2,3-c] system in the other. Structure proof was accomplished by an unequivocal synthesis of one of the [2,3-c] derivatives.     

Some derivatives of pyrimido [5,4-b]quinoline

10-Chloro-2,4-dioxo derivatives of pyrimido[5,4-b]quinoline have been synthesized, and nucleophilic substitution reactions in these compounds have been studied.     

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.