Polyfunctional fluoroalkyl-containing carbonyl compounds in the synthesis of heterocycles

Efficient procedures for the regioselective synthesis of fluoroalkyl-containing threefive-, six-, and seven-membered heterocycles as well as of related fused compounds, namely, α,β-epoxyketones, α,β-aziridinylketones, pyrazoles, pyrazolines, isoxazolines, 1,2-dithiolenes, amino- and mercaptopyrimidines, Δ^3,5-2-thioxo-1,3,2-thiazaphosphorines, Δ^3,5-2-thioxo-1,3,2-oxazaphosphorines, 2,3-dihydro-1,4-diazepines, azirino[1,2-a]quinoxalines, benzo[b]-and naphtho[2,3-b]-1,4-diazepines, and triazolopyridazines, which have been developed by the authors and coworkers, are summarized. The α- and β-functionalized fluoroalkylcontaining carbonyl compounds (β-diketones, β-ketoesters, their salts, regioisomeric β-aminovinyl ketones, β-aminovinylthiones, β-hydroxyketones, α,β-enones, and their halogen derivatives) were used as synthons in the processes of formation of the above-mentioned heterocycles. Dedicated to the memory of Academician I. Ya. Postovskii on his 100th birthday. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1279–1286, July, 1998.     

Acylation of [B12H12]2− dianion by carboxylic acid halides

The sodium salt of [B₁₂H₁₂]²⁻ dianion reacts with carboxylic acid halides to give a mixture of B-acylated product [B₁₂H₁₁COR]²⁻ and an unstable intermediate, the latter undergoing hydrolysis to form [B₁₂H₁₁OH]²⁻. The ratio of the products formed depends on the nature of the radical R. The reaction mechanism was studied by NMR spectroscopy. A number of novel [B₁₂H₁₁COR]²⁻ compounds were synthesized; their structures were confirmed by NMR and IR spectral data. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 980–985, May, 1998.     

Formation of 2-oxatricyclo[4.3.1.03,8]decanes in intramolecular cyclization of α-halobicyclo[3.3.1]nonanones

Transformations of α-chloro- and α-bromobicyclo[3.3.1]nonanones under conditions of the Favorskii reaction were studied. The interaction of dihalodiketones with MeONa gives 2-oxatricyclo[4.3.1.0^3.8]decane (oxaprotoadamantane) derivatives as a result of intramolecular cyclization, whereas 3-bromobicyclononanone undergoes only nucleophilic substitution of bromine. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 342–344, February, 1997.     

Heterocyclic analogs of 5,12-naphthacenequinone 7*. Synthesis of naphtho-[2,3-f]isatin-5,10-dione derivatives

On chlorination of 4,11-dimethoxynaphtho[2,3-f]indole-5,10-dione with sulfuryl chloride in chloroform, its mono-, di-, and trichloro derivatives are formed depending on the conditions. Hydrolysis of the di- and trichloro derivatives gives a new polycondensed derivative of isatin, 4,11-dimethoxynaphtho-[2,3-f]isatin-5,10-dione. Its demethylation occurs effectively on extended heating with HBr in acetic acid and leads to 4,11-dihydroxynaphtho[2,3-f]isatin-5,10-dione (4,11-di-hydroxynaphtho[2,3-f]indole-2,3,5,10-tetraone). *For Communication 6 see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1532–1536, October, 2008.     

The mannich reaction in the synthesis of N,S-containing heterocycles 4. Aminomethylation of 6-amino-3,5-dicyano-1,4-dihydropyridine-2-thiolates: A convenient regioselective route to 3,5,7,11-tetraazatricyclo[7.3.1.02,7]tridec-2-ene derivatives

Treatment of N-methylmorpholinium 4-R-6-amino-3,5-dicyano-1,4-dihydropyridine-2-thiolates (R = 2-ClC₆H₄ and 2-MeOC₆H₄) with primary amines in the presence of an excess of formaldehyde gave 13-R-8-thioxo-3,5,7,11-tetraazatricyclo[7.3.1.0^2,7]tridec-2-ene-1,9-dicarbonitrile derivatives in high yields (66–95%). In a similar way, aminomethylation of 3-R-10-amino-7,11-dicyano-9-aza-3-azoniaspiro[5.5]undeca-7,10-diene-8-thiolates (R = Me and Et) afforded 1′-alkyl-8-thioxospiro[3,5,7,11-tetraazatricyclo[7.3.1.0^2,7]tridec-2-ene-13,4′-piperidine]-1,9-dicarbonitriles in 43–91% yields. Alternatively, these compounds were obtained by multicomponent cyclocondensation of N-alkylpiperidin-4-ones, cyanothioacetamide, primary amines, and aqueous formaldehyde. The starting 3-R-10-amino-7,11-dicyano-9-aza-3-azoniaspiro[5.5]undeca-7,10-diene-8-thiolates were prepared by a new method from N-alkylpiperidin-4-ones and cyanothioacetamide. The structure of 5,11-bis(4-ethoxyphenyl)-13-(2-methoxyphenyl)-8-thioxo-3,5,7,11-tetraazatricyclo[7.3.1.0^2,7]tridec-2-ene-1,9-dicarbonitrile was examined by X-ray diffraction analysis. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1014–1022, May, 2007.     

Reaction of α,α-, α,α′-dihalothiones with 8-mercaptoquinolinium halides as a route to tetrahydro-1,4-thiazinoquinolinium halides

The reaction of 8-mercaptoquinolinium bromide with 1,3-dibromopropane-2-thione or 3,3-dibromobutane-2-thione in methanol gave the 2-bromomethyl-2-mercaptotetrahydro-1,4-thiazino[2,3,3,4-i,j]quinolinium and 3-bromo-2-mercapto-2,3-dimethyltetrahydro-1,4-thiazino[2,3,3,4-i,j]quinolinium bromides which readily exchanged the Br⁻ anion for ClO ₄ ⁻ upon treatment with sodium perchlorate in methanol. Oxidation of the 3-bromo-2-mercapto-2,3-dimethyltetrahydro-1,4-thiazino[2,3,3,4-i,j]-quinolinium bromide by selenium dioxide gave 2,2-dithiobis(3-bromo-2,3-dimethyltetrahydro-1,4-thiazino[2,3,3,4-i,j]quinolinium) bromide. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1720–1723, November, 2006.     

Heterocyclic analogs of 5,12-naphthacenequinone 8.* Synthesis of furano-anthraquinones

During the condensation of 2,3-dichloroquinizarine with methyl pivaloylacetate in the presence of potassium carbonate in dimethyl sulfoxide the main reaction products are derivatives of angular 3-pivaloylanthra[1,2-b]furan-2,6,11(3H)-trione (about 70%) and anthra[2,1-d][1,3]dioxole-6,11-dione (15%), whereas the yield of the targeted linear methyl 2-tert-butyl-4,11-dihydroxyanthra[2,3-b]furan-5,10-dione-3-carboxylate is only 2%. Methods are developed for modification of the obtained 3-pivaloylanthra[1,2-b]furan-2,6,11(3H)-trione, making it possible to use it for the synthesis of the tert-butyl derivatives of linear anthra[2,3-b]furan-5,10-dione or angular anthra[1,2-b]furan-6,11-dione. *For Communication 7 see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 191–202, February, 2009.     

Synthesis and structures of pyridoannelated 1,2,3,4-tetrazine 1,3-dioxides

Treatment of 2- and 4-amino-3-(tert-butyl-NNO-azoxy)pyridines with nitrating agents (N₂O₅or NO₂BF₄) afforded the first representatives of pyridoannelated 1,2,3,4-tetrazine di-N-oxides, viz., pyrido[2,3-e][1,2,3,4]tetrazine 1,3-dioxide (9), 7-nitropyrido[2,3-e][1,2,3,4]tetrazine 1,3-dioxide (10), and pyrido[3,4-e][1,2,3,4]tetrazine 2,4-dioxide (11). These compounds were studied by ¹H, ¹³C, and ¹⁴N NMR spectroscopy. The 1:1 complex of compound 10 with benzene was studied by X-ray diffraction analysis.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2471–2477, November, 2004.     

The investigations in 2,3′-biquinoline series. 25*. Synthesis of 4-(2-quinolinyl)-pyrrolo[1,2-<Emphasis Type="Italic">a</Emphasis>]quinolines and 4-(2-quinolyl)-imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]quinolines

A method has been developed for the synthesis of 4-(2-quinolinyl)-1,2,3,3a-tetrahydropyrrolo-[1,2-a]quinolines based on the 1,3-dipolar cycloaddition reaction of α,β-unsaturated carbonyl compounds to 2,3′-biquinolinium salts. Oxidation in benzene using MnO₂ gave 4-(2-quinolinyl)-pyrrolo[1,2-a]quinolines. It was found that a side product of the 1,3-dipolar cycloaddition is 7,14-di-benzoyl-6,13-di(2-quinolyl)-6a,7,13a,14-tetrahydro-7a,14a-diazadibenzo[a,h]anthracene. Reaction of 1′-phenacyl-2,3′-biquinolinium salts with hydroxylamine in acetic acid gave 4-(2-quinolyl)imidazo-[1,2-a]quinolines. *For Communication 24 see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 433–439, March, 2009.     

Synthesis and reactivity of thieno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridine-2,3-diamines

It has been established that the interaction of N¹-(2-hydroxyphenylmethylthieno[2,3-b]pyrid-3-yl)arylamides with hydrazine hydrate leads to thieno[2,3-b]pyridine-2,3-diamines. It was shown that the reaction of the latter with acetylacetone and acetoacetic ester occurs regioselectively at the amino group in position 3 of the thiophene ring. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1400–1408, September, 2007.     

Interaction of Cucurbit[n = 6∼8]urils and Benzimidazole Derivatives

The structures and optical properties of host–guest complexes produced from cucurbit[n = 6–8]urils and some benzimidazole derivatives have been investigated by ¹H NMR spectroscopy, electronic absorption spectroscopy and fluorescence spectroscopy. The experimental results reveal that calculations of A∼N_Q[n]/N_guest and I_f∼N_Q[n]/N_guest for the same association complex both support a good fit to an identical binding model. In particular, the A∼N_Q[n]/N_guest, I_f∼N_Q[n]/N_guest calculations and the ¹H NMR determinations for three Q[6]–ge(1∼3) complexes and three Q[8]–ge(1∼3) complexes all support a binding model of 1:1 and 1:2 respectively.     

Acetylenchemie, 33. Mitt.: Synthese von 2-substituierten Dihydrofuro[2,3-b]chinolinen

Summary The reaction of 3-iodo-4-methoxy-2(1H)-quinolinone (1) and 3-iodo-4,6,8-trimethoxy-2(1H)-quinolinone (2) with 2-methyl-3-butyn-2-ol under modified Heck-conditions gave the 2-substituted derivatives 2-(1-hydroxy-1-methylethyl)-4-methoxyfuro[2,3-b]-quinoline (3) and 2-(1-hydroxy-1-methylethyl-4,6,8-trimethoxyfuro[2,3-b]-quinoline (4). By a subsequent hydrogenation-reaction with a homogeneous catalyst (PtO₂/Rh₂O₃), the furoquinoline-derivatives yielded the dihydrofuro-[2,3-b]quinolines, identified as 2-(1-hydroxy-1-methylethyl-4-methoxy-2,3-dihydrofuro[2,3-b]quinoline (5) (racemic platydesmine) and 2-(1-hydroxy-1-methylethyl)-4,6,8-trimethoxy-2,3-dihydrofuro-[2,3-b]quinoline (6) (racemic precursor of O⁴-methylptelefolonium salt).

     

Mechanism of dehydration of 2-CH2R-and 2-CHR2-4-hydroxy-Δ2-thiazolines as intermediates in the Hantzsch thiazole synthesis and factors impeding the synthesis of 2-Me-, 2-Ar-, and 2-Het-substituted thiazoles and thiazolo[5,4-b]indoles

Based on the results of studies of the deuterium exchange and dehydration of 4-hydroxy-Δ²-thiazolines and 2-R-4-acetyl-8b-hydroxy-3a,8b-dihydro-4H-thiazolo[5,4-b]indoles containing the α-methylene (methine) unit at the C(2) atom, the mechanism of dehydration of these compounds generated as intermediates in the Hantzsch synthesis of thiazoles and 2-R-4-acetyl-4H-thiazolo[5,4-b]indoles was proposed. This mechanism includes an additional step of the formation of the corresponding Δ³-thiazolines. According to the results of quantum chemical calculations, this is energetically more favorable than the dehydration in terms of the commonly accepted mechanism. In some cases, an acidic medium impedes the dehydration of 4-hydroxy-Δ²-thiazolines or their cyclic analogs. The proposed mechanism provides an explanation for the empirical data on the differences in the reactivities of both thioamides and α-haloketones, which have remained unexplained in terms of the commonly accepted mechanism. The spontaneous thiazole synthesis is virtually impossible starting from thioamides of aromatic or heteroaromatic acids and α-haloketones bearing electron-withdrawing α′ substituents or cyclic bromoindoxyl-type haloketones. In the thiazole synthesis from these starting components, it is expedient to perform dehydration under basic catalysis. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1394–1402, July, 2007.     

Tandem transformations of tetrahydropyrrolo[3,2-<Emphasis Type="Italic">c</Emphasis>]pyridines under the action of dimethyl acetylenedicarboxylate. A novel route to pyrrolo[2,3-<Emphasis Type="Italic">d</Emphasis>]azocines

Reactions of substituted tetrahydropyrrolo[3,2-c]pyridines with dimethyl acetylenedicarboxylate in protic and aprotic solvents were studied. A novel single-step method for the synthesis of pyrrolo[2,3-d]azocine derivatives was developed. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2513–2519, November, 2005.     

Study of the Products of Iodocyclization of 4-Allyl-5-phenyl-1,2,4-triazole-3-thione

The interaction of 4-allyl-5-phenyl-1,2,4-triazole-3-thione with iodine proceeds with the formation of a mixture of 6-iodomethyl-3-phenyl-5,6-dihydrothiazolo[2,3-c]-1,2,4-triazole and 6-iodo-3-phenyl-6,7-dihydro-5H-1,2,4-triazolo[3,4-b]-1,3-thiazine. The structures of the cyclization products obtained were established on the basis of the ¹H NMR spectra of their dehydroiodinated derivatives. 6-Methyl-3-phenylthiazolo[2,3-c]-1,2,4-triazole, 3-phenyl-5H-1,2,4-triazolo[3,4-b]-1,3-thiazine, and 3-phenyl-7H-1,2,4-triazolo[3,4-b]-1,3-thiazine are formed on eliminating HI from the cyclization products.     

Synthesis and transformations of 3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridines

Reactions of 2,5-dimethoxytetrahydrofuran with 3-aminothieno[2,3-b]pyridines afford a number of substituted 3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridines. The possibility of the reaction and the yield of the product are determined by the character of a substituent in position 2 of thieno[2,3-b]pyridine. The Curtius rearrangement of 2-acylazido-3(1H-pyrrol-1-yl)thieno[2,3-b]pyridines yields 4,5-dihydropyrido[3",2":4,5]thieno[2,3-e]pyrrolo[1,2-a]pyrazin-4-ones. The molecular and crystal structures of ethyl 4-methoxymethyl-6-methyl-3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridine-2-carboxylate were determined by X-ray diffraction analysis.     

Synthesis of derivatives of a new heterocyclic system,indolo[2,3-f][1,7]naphthyridine

3-(N"-Aryl-N"-chloroacetyl)amino-2-formylindoles were converted into 3-amino-1-aryl-2-oxo-1,2-dihydropyrido[3,2-b]indoles, which were used to synthesize derivatives of a new heterocyclic system, namely, indolo[2,3-f][1,7]naphthyridine. The structures of the resulting compounds were proved by IR and ¹H NMR spectroscopy and mass spectrometry.     

Molecular and crystal structure of a new compound methyl-18R-13-isopropyl-10a,7-dimethyl-4-oxo-1-oxahexacyclo×[12.4.0.05a,4a.013,1201,1a.010a,6a]heneicosane-7-carboxylate

Synthesis is performed and the molecular structure is analyzed of methyl-18R-13-isopropyl-10a,7-dimethyl-4-oxo-1-oxahexacyclo[12.4.0.0^5a,4a.0^13,12.0^1,1a.0^10a,6a]heneicosane-7-carboxylate II. Compound II C₂₇H₄₀O₄ crystallizes in orthorhombic symmetry with cell parameters: a = 11.9915(15) ?, b = 12.1674(16) ?, c = 15.8094(17) ?, P2₁2₁2₁, Z = 4, d = 1.234 g/cm³. Original Russian Text Copyright ? 2009 by I. E. Smirnova, E. V. Tret’yakova, O. B. Kazakova, Z. A. Starikova, and I. V. Fedyanin __________ Translated from Zhurnal Strukturnoi Khimii, Vol. 50, No. 2, pp. 391–392, March–April, 2009.     

[3,4]-annulated pyrroles 1. Polynuclear heterocyclic systems based on pyrrolo[3,4-d]pyrimidine-2,4-dione

The intramolecular electrophilic substitution in 6-functionalized 1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-diones was used for the synthesis of pyrimido[4′,5′:3,4]-pyrrolo[1,2-a]quinoxaline-8,10(7H,9H)-dione, pyrimido[4′,5′:3,4]pyrrolo[2,1-c][1,2,4]benzo-triazine-8,10(7H,9H)-dione, and 2H-pyrimido[4′,5′:3,4]pyrrolo[1,2-a]indole-2,4,11(1H, 3H)-trione derivatives. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2180–2185, December, 2006.     

Phosphorylthioacetamides in the synthesis of annulated quinoxalines

Diethoxyphosphorylthioacetamide in the reaction with 2,3-dichloroquinoxaline acted as a thionating reagent, giving diethoxyphosphorylacetonitrile and 2-chloro-3-[(3-chloro-2-quinoxalinyl)thio]quinoxaline. Reactions of phosphorylthioacetamides with N-methylquinoxalinium iodide in alcohol media in the presence of a base proceeded stereoselectively to afford cis-3-phosphoryl-1,3,3a,4,9,9a-hexahydro-2H-pyrrolo[2,3-b]quinoxaline-2-thiones. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1010–1013, May, 2007.