Benzindoles XII. Spectra and three-dimensional structures of [6,7]- and [4,5]benzoskatolideneacetones

It was found by means of their ER, UV, and PMR spectra that [6,7]benzoskatolideneacetones have a side chain in the trans-s-cis form, whereas the [4, 5] isomers have a side chain in the cis-s-cis form. It was concluded from the integral intensities of the bands of the vibrations of the double bond (A_C=C)) and the parameters of the UV spectra that the investigated molecules have a planar structure. The A_C=C) integral intensities in the IR spectra exceed the previously observed values and, in the case of [6,7]benzoskatolideneacetones, reach ～6· 10⁴ mole^?1liter·cm^?2.     

Benzindoles. 21. Nitration of 3-formyl[4, 5]-and 3-formyl [6,7] benzindoles

It was established that products of monosubstitution of 4-nitro- and 7-nitro-3-formyl[4,5] benzindoles and products of disubstitution of 4,8-dinitro- and 7,8-dinitro-3-formyl [4,5] benzindoles are formed in low yields in the nitration of 3-formyl [4,5]benzindole with sodium nitrate in concentrated sulfuric acid. Similar nitration of 3-formyl [6,7] benzindole leads to 9-nitro- and 5, 6-dinitro-3-formyl [6,7]benzindoles. The 3-formylnitrobenzindoles obtained were converted to nitrovinyl derivatives by condensation with nitromethane.See [1] for Communication [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 949–955, July, 1980.     

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.     

The synthesis of ω-dialkylaminoalkylaminopyrazino[2,3-d]-, pyrido[2,3-d]-, imidazo[4,5-c]- and imidazo[4,5-d]pyridazines

The synthesis of 5-chloro-8-(ω-dialkylaminoalkylamino)pyrazino[2,3-d]pyridazine (II) proceeded smoothly when 5,8-dichloropyrazino[2,3-d]pyridazine (I) was allowed to react with ω-dialkylaminoalkylamines. Similarly, the reaction of 5,8-dichloropyrido[2,3-d]pyridazine (IV) with ω-dialkylaminoalkylamines gave the two expected products 8-chloro-5-(ω-dialkylaminoalkylamino)pyrido[2,3-d]pyridazine (V) and 5-chloro-8-(ω-dialkylaminoalkylamino)pyrido[2,3-d]pyridazine (VI) in a 2:3 ratio. 4,7-Dichloroimidazo[4,5-d]pyridazine (XII) was found to be much less reactive towards nucleophilic substitutions and more vigorous conditions resulted in disubstituted products (XIII). 7-Chloroimidazo[4,5-c]pyridazine (XVIII) was also found to be much less reactive towards nucleophilic substitution. In both of these cases one of the imidazole nitrogen atoms was blocked by a tetrahydropyranyl group which increased the reactivities and led to the desired monosubstituted products XVII from XII and in the latter case the expected products (XIX).     

Imidazo [4,5-c] - and [4,5-6] pyridines

The synthesis of novel imidazo[4,5-c]pyridines 11-13 and imidazo[4,5-b]pyridines 18-20 is described using 2 as the starting material. The synthesis is generally applicable for the introduction of a wide variety of substituents.     

A study of nitrogen- and oxygen-containing heterocycles. 42. Pyrimido[4,5-b]- and pyrido[2,3-b]-1,4-benzoxazepines

The reaction of o-haloamino derivatives of pyrimidine and pyridine with o-hydroxy-benzaldehyde and its derivatives leads to the formation of tricyclic 1,4-oxazepine systems. Syntheses are reported for derivatives of pyrimido[4,5-b]- and pyrido[2, 3-b]-1,4-benzoxazepines as well as of their 5,6-dihydro derivatives. The properties and structures of these compounds were studied.For Communication 41, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 122–125, January, 1985.     

Furopyridines. XXIX. Reactions of furo[2,3-b:4,5-c‘]-, -[3,2-b:-4,5-c’]-, -[2,3-c:4,5-c‘]- and -[3,2-c:3,2-c’]dipyridine

Furo[2,3-b:4,5-c‘]- 1a , -[3,2-b:4,5-c’]- 1b , -[2,3-c:4,5-c‘]- 1c and -[3,2-c:4,5-c’]dipyridine 1d were derived to the N-oxides 2a-d , N‘-oxides 2′b , 2′c or N,N’-dioxide 3b-d by N-oxidation with m-chloroperbenzoic acid. Chlorination of these N-oxides, N′-oxide and N,N′-dioxides with phosphorus oxychloride afforded compounds chlorinated at the α-position(s) to the ring nitrogen 4a-d , 4′c , 14b-d and 14′b . Acetoxylation of N-oxides 2a-d and 2′c with acetic anhydride gave the corresponding pyridone compounds 6a-d and 6′c in good yields, while the acetoxylation of N,N′-dioxides gave a complex mixture from which no compound could be isolated. Cyanation of 2a-d, 2′c and 3b-d with trimethylsilyl cyanide yielded the cyano compounds 7a-d , 7′c , cyano-N-oxides 15b-d and dicyano compounds 15′c and 15′d . Monocyano compounds 7a-d and 7′c were converted to the imino esters 8a-d and 8′c by treatment with sodium ethoxide. Imino esters were derived to the carboxylic esters 9a-d and 9′c , from which the corresponding alde hydes 10a-d and 10′c were obtained by reduction with diisobutylaluminum hydride. Dicyanide 15′c was converted to dialdehyde 19 by the treatment with sodium ethoxide, and the subsequent hydrolysis of the imino ester and reduction of the carboxylic ester with diisobutylaluminum hydride.     

The synthesis of lmidazo[4,5-d] pyridazines. VI. v-Triazolo[4,5-d] pyridazines,pyrazino[ 2,3-d ] pyridazines and 7H-Imidazo [4,5-d] tetrazolo[ 1,5-b] pyridazine

Several pyridazines have been prepared as intermediates in the synthesis of monosubstituted imidazo[4,5-d]pyridazines, monosubstituted v-triazoIo[4,5-d]pyridazines and monosubstituted pyrazino [2,3d] pyridazines. The new ring system, 7H-imidazo[4,5-d]tetrazolo[l,5-b] pyridazine (XIV) has been prepared unsubstituted. Furthermore, unsubstituted imidazo[4,5-d]pyridazine (XI) has been prepared. Calculations for XI and XIV were made by approximate SCF LCAO-MO with CNSO II theory.     

Synthesis of imidazo[4,5-b]- and [4,5-c]pyridines

2-Arylimidazo[4,5-b]- and [4,5-c]pyridines have been prepared by treatment of the appropriate 2,3- or 3,4-diaminopyridine with an aromatic carboxylic acid in the presence of polyphosphoric acid. Other derivatives have been prepared by similar cyclisation of diaminopyridines using triethyl orthoformate, urea, thiophosgene and thiourea and the properties of some N-oxides have been investigated. A number of the arylimidazopyridines have been screened for mutagenicity.     

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 .     

Microwave assisted synthesis of 2,3-dihydro-4H-benzo[4,5]thiazolo[3,2-a]furo[2,3-d]pyrimidin-4-ones and 6,7-dihydro-5H-furo[2,3-d]thiazolo[3,2-a]pyrimidin-5-ones using Mn(OAc)3

2-Hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one 2a and 7-hydroxy-5H-thiazolo[3,2-a]pyrimidin-5-one 2b, were obtained in high yields under mild conditions from the cyclization reactions of bis-(2,4,6-trichlorophenyl) malonate and 2-aminobenzothiazole or 2-aminothiazole, respectively. A new class of compounds, 2,3-dihydro-4H-benzo[4,5]thiazolo[3,2-a]furo[2,3-d]pyrimidin-4-ones and 6,7-dihydro-5H-furo[2,3-d]thiazolo[3,2-a]pyrimidin-5-ones, were synthesized via the microwave assisted radical addition of compounds 2a and 2b to various alkenes using manganese(III) acetate. A preliminary acetylcholine esterase (AchE) inhibition test of compound 4e showed excellent (92%) inhibitory potential, comparable with the standard drug Donapezil®.     

Facile preparation of benzo[4,5]thieno[2,3-b]pyridines and naphtho[b-4,5]thieno[2,3-b]pyridines via the reaction of Barton esters and benzynes

Titled compounds were prepared in a one-pot synthesis by generating symmetrically substituted benzyne intermediates by the diazotization of anthranilic acids in the presence of Barton esters. Unsymmetrically substituted aryne either gave mixtures of regioisomers or failed. However, nitro and methyl derivatives of titled compounds could be obtained as single products using appropriately substituted Barton esters.     

Enolethers. XX . Synthesis of azepino[4,5-b]quinoxalines and pyridopyrazino[2,3-d]azepines

1,6-Diethoxy-1,5-hexadiene-3,4-dione ( 1 ) reacts with primary amines 3 and ammonia respectively in a molar ratio of 1:1 to give mainly aminoalkyl- and small amounts of bis(aminoalkyl)-1,5-hexadiene-3,4-diones 4 and 2 , respectively. On heating in dichlorobenzene above 150° the mixtures of 2 and 4 cyclize to yield 1-alkyl-1H-azepine-4,5-diones 5 by elimination of ethanol or amine. 3H-3-Alkylazepino[4,5-b]-quinoxalines 7, 8, 10 and 12 are easily accessible by condensation of the diketones 5a and b with various substituted o-phenylenediamines 6, 9 and 3,3′,4,4′-tetraaminobiphenyl ( 11 ) in p-xylene or n-butanol. 8-Isopropylpyridopyrazino[2,3-d]azepines 14 were obtained by condensation of 5b with pyridinediamines 13 in p-xylene. The azepine-4,5-diones 5a-c can be hydrogenated selectively by sodium borohydride in ethanol at room temperature to give the azepin-4-ol-5-ones 15a-c .     

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 .     

Aromatic derivatives of 1H-2,3-dihydropyrazolo[4,5-b]-1,5-diazepine

Aromatic derivatives of 1H-2,3-dihydropyrazole[4,5-b]-1,5-diazepine were obtained by the reaction of 1-phenyl-3-methyl-4,5-diaminopyrazole with chalcones and acetylarenes, catalyzed by acetic or sulfuric acid. The seven-membered ring in these compounds has a conformation of the boat type. The IR, UV, PMR, and mass spectra of the compounds are discussed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 363–369, March, 1987.     

The synthesis of the monomethylbenzo[2,3]phenanthro-[4,5-bcd]thiophenes

The synthesis of the potentially mutagenic 1-methyl- (11), 3-methyl- (12), 4-methyl- (21), 5-methyl- (27), 7-methyl- (58), 8-methyl- (61), 9-methyl- (59) and 10-methylbenzo[2,3]phenanthro[4,5-bcd]thiophene (60) is reported.     

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. 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.