NMR spectra of cyclic nitrones. 4. Synthesis and 13C NMR spectra of 4H-imidazole N-oxides and N,N-dioxides

4H-Imidazole 1,3-dioxides and 4H-imidazole 3-oxides were obtained by oxidation of 1-hydroxy-3-imidazoline 3-oxides and 1-hydroxy-3-imidazolines with lead and manganese dioxides or the stable nitroxyl radical, while 4H-imidazole 1-oxides were obtained by thermal decomposition of 1-acetoxy-3-imidazoline 3-oxides. Facile oxidation of the ethyl group in 5-ethyl-4H-imidazole 1,3-dioxide and the formation of 5-acetyl-4H-imidazole 1,3-dioxide and 5-acetyl-4H-imidazole 3-oxide were observed. It is shown that a strictly determined region of chemical shifts of the C(₂), C(₅), and C(₄) atoms is characteristic for each group of 4H-imidazole N-oxides in the ¹³C NMR spectra; this makes it possible to clearly establish the position of the N-oxide oxygen atom.See [1] for Communication 3.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1640–1648, December, 1988.     

Diels–Alder Reactions with Cyclic Sulfones: VII. Synthesis of 1-Benzothiophene 1,1-Dioxide Derivatives

5-Arylmethylene-2,2-dimethyl-1,3-dioxane-4,6-diones reacted with 5-isopropenyl-2,3-dihydrothio-phene 1,1-dioxide to give the corresponding ortho-addition products, 5-aryl-2',2',7-trimethyl-3,3a,5,6-tetra-hydro-2H-spiro[1-benzothiophene-4,5'-[1,3]dioxane]-4',6'-dione 1,1-dioxides. Their aminolysis resulted in opening of the 1,3-dioxane ring and formation of 4-carbamoyl-7-methyl-2,3,3a,4,5,6-hexahydro-1-benzo-thiophene-4-carboxylic acid 1,1-dioxide whose structure was determined by X-ray analysis. Reactions of the spiro adducts with amines and hydrazine hydrate afforded the corresponding mono- or dicarboxylic acid monoamides (hydrazide).     

The first synthesis and X-ray structures of polyfluorinated 1,2-, 2,3- and 2,4a-dihydro-1,3-diazafluorenes

Acetic acid-catalyzed condensation of 2-amino-3-(1-imino-2,2,2-trifluoroethyl)-1,1,4,5,6,7-hexafluoroindene (1b) with acetone and cyclopentanone gives 5,6,7,8,9,9-hexafluoro-2,2-dimethyl-4-trifluoromethyl-2,3-dihydro-1,3-diazafluorene (2a) and 5,6,7,8,9,9-hexafluoro-4-trifluoromethyl-2,3-dihydro-1,3-diazafluorene-2-spiro-1′-cyclopentane (3a) together with small amounts of 5,6,7,8,9,9-hexafluoro-2,2-dimethyl-4-trifluoromethyl-1,2-dihydro-1,3-diazafluorene (2b) and 5,6,7,8,9,9-hexafluoro-4-trifluoromethyl-1,2-dihydro-1,3-diazafluorene-2-spiro-1′-cyclopentane (3b), respectively. When acted upon by (CH₃)₂SO₄ compounds 2, 3 were converted into corresponding fluorine-containing 1-methyl-1,2-dihydro-1,3-diazafluorenes 6, 7. 4a-Chloro-5,6,7,8,9,9-hexafluoro-2,2-dimethyl-4-trifluoromethyl-2,4a-dihydro-1,3-diazafluorene (8) has been synthesized by the interaction of compound 2 with SOCl₂. Solution of compound 2 as well as 8 in CF₃SO₃H-CD₂Cl₂ generated 5,6,7,8,9,9-hexafluoro-2,2-dimethyl-4-trifluoromethyl-1,2,3,4-tetrahydro-1,3-diazafluorene-4-yl cation (2c). The structures of compounds 2, 3, 6-8 have been determined by single crystal X-ray diffraction.     

The reactions of thiosemicarbazides and 5-halovalerophenones

5-Halovalerophenones reacted with substituted thiosemicarbazides affording two different heterocyclic ring systems. Reactions with 4-substituted thiosemicarbazides gave 3-aryl-4,5,6,7-tetrahydro-1H-1,2-diazepine-1-carbothioamides whereas reactions with 2,4-dimethylthiosemicarbazide gave hexahydro-1,3-dimethyl-8a-aryl[1,2,4]triazolo[1,5-a]pyridine-2(3H)-thiones.     

Reaction of sulfene with heterocyclic N,N-disubstituted α-aminomethyleneketones. IX. Synthesis of 1,2-oxathiino[6,5-e]indole derivatives

The polar 1,4-cycloaddition of sulfene to N,N-disubstituted 5-aminomethylene-1,5,6,7-tetrahydro-1-methylindol-4-ones occurred only in the case of aliphatic N-substitution to give, generally in good yield, 4-dialkylamino-3,4,5,6-tetrahydro-7-methyl-7H-1,2-oxathiino[6,5-e]indole 2,2-dioxides IV. Full aromatization of IVa (4-NR₂ = dimethylamino) with DDQ in refluxing benzene gave in low yield 7-methyl-7H-1,2-oxathiino-[6,5-e]indole 2,2-dioxide, whereas the same reaction of IVe (4-NR₂ = morpholinyl) with excess DDQ afforded in low yield 7-methyl-4-morpholinyl-7H-1,2-oxathiino[6,5-e]indole 2,2-dioxide.     

3-acyl-1,5-benzodiazepines in the reactions of 5,5-dimethyl-2-formylcyclohexane-1,3-dione with certain 1,2-diaminobenzenes

Reaction of 5,5-dimethyl-2-formylcyclohexane-1,3-dione with 4-methyl-, 4-benzoyl-, and 4-nitro-1,2-diaminobenzenes gave the corresponding 2-(2-amino-4-methylphenylaminomethylene)-, 2-(2-amino-5-benzoylphenylaminomethylene)-, and 2-(2-amino-5-nitrophenylaminomethylene)-5,5-dimethylcyclohexane-1,3-diones. When treated with hydrochloric acid, they cyclize to 7-methyl-, 8-benzoyl-, and 8-nitro-3,3-dimethyl-2,3,4,5-tetrahydro-1H-dibenzo[b,e][1,4]diazepinon hydrochlorides. Under hydrolytic conditions the salts of 3,3,7-trimethyl-2,3,4,5-tetrahydro-1H-dibenzo[b,e][1,4]diazepinone and 3,3-dimethyl-2,3,4,5-tetrahydro-1H-dibenzo[b,e][1,4]diazepinone undergo the C₁₁−N₁₀ bond cleavage to give N-(2-aminophenyl)- and N-(2-amino-5-methylphenyl)-substituted 3-amino-2-formyl-5,5-dimethylcyclohex-2-enones. Ring opening of the hydrochlorides of 8-benzoyl-, and 3,3-dimethyl-8-nitro-2,3,4,5-tetrahydro-1H-dibenzo[b,e][1,4]diazepinones occurs at the C−N₅ bond and gives the starting enamines. Riga Technical University, Riga LV-1658, Latvia; Translated from Khimiya Geterotsiklicheskikh Soedinenii, N. 5, pp. 696–700, May, 1999.     

Synthesis of 6-imino-5-tetrahydro-1H-2-pyrrolylidenhexahydro-2,4-pyrimidinediones as intermediates for the synthesis of C-azanucleosides

The method for the synthesis of 6-imino-5-tetrahydro-1H-2-pyrrolylidenhexahydro-2,4-pyrimidinediones is described. It is shown that the reaction of phosphorus trichloride, 2-pyrrolidones and 6-aminopyrimidines brings to condensation producing 6-imino-5-tetrahydro-1H-2-pyrrolylidenhexahydro-2,4-pyrimidinediones as intermediates for the synthesis of C-azanucleosides. The reaction of 6-imino-1,3-dimethyl-5-tetrahydro-2-pyrrolylidenhexahydro-2,4-pyrimidinedione with benzoyl chloride produces 10-benzoyl-2,4-dimethyl-6-phenyl-1,2,3,4,8,9-hexahydropyrimido[5,4-e]pyrrolo[1,2-c]pyrimidine-1,3-dione. A method for the selective reduction of the carbomethoxy group of methyl 5-(4-imino-1,3-dimethyl-2,6-dioxohexahydro-5-pyrimidinyliden)-2-pyrrolidine carboxylate by system NaBH₄/1,4dioxane/CoCl₂/PEG-400 is described.     

Three component condensation of 6-quinolylamine with aromatic aldehydes and cyclohexyl 1,3-diketones

A three component condensation of 6-quinolylamine with 4-bromo-or 4-methoxybenzaldehyde, and 1,3-cyclohexanedione or dimedone gave 12-(4-bromophenyl)-and 12-(4-methoxyphenyl)-9,9-dimethyl-8,9,10,12-tetrahydro-7H-benzo[b][4,7]phenanthrolin-11-ones. The reaction intermediates obtained were N-arylmethylene-6-quinolylamines, 2-arylmethylenebis(1,3-cyclohexanediones), 3-(6-quinolylamino)-2-cyclohexenone, and 5,5-dimethyl-3-(6-quinolylamino)-2-cyclohexenone. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No 6, pp. 877–885, June, 2007.     

Ringerweiterung von sechs- zu neungliedrigen Heterocyclen: Umsetzung von 3-(Dimethylamino)-2,2-dimethyl-2H-azirin mit 3,4-Dihydro-2H-1,2,4-benzothiadiazin-3-on-1,1-dioxiden

Ring Enlargement of Six- to Nine-Membered Heterocycles: Reaction of 3-(Dimethylamino)-2,2-dimethyl-2H-azirine with 3,4-Dihydro-2H-1,2,4-benzothiadiazin-3-one 1,1-Dioxides Reaction of 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1 ) and N-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazin-3-one 1,1-dioxides ( 4 ) in CHCl₃ yields 3-(dimethylamino)-4,5,6,7-tetrahydro-1,2,5,7-benzothiatriazonin-6-one 1,1-dioxides 5 , a novel nine-membered heterocyclic system, by ring enlargement (Schemes 2 and 4). In refluxing MeOH, the heterocycle 5a rearranges to give the N-[1-methyl-1-(1,1-dioxo-4H-1,2,4-benzothiadiazin-3-yl)ethyl]-N′, N′-dimethylurea 10 . The three isomeric 2-(methylamino)benzenesufonamides 8,9 , and 11 (Scheme 3) are obtained by naBH₄ reduction of 5a and 10 , respectively. Mechanisms for the thermal isomerization 5a → 10 and the NaBH₄ reduction of 5a are proposed in Schemes 5 and 6.     

Oxidation of 4,7-phenanthroline derivatives

Oxidation of 1,3-diphenyl-4,7-phenanthroline with potassium permanganate in alkaline medium results in transformation of the 4,7-phenanthroline ring system into 1,8-diaazafluorenone. Oxidation of 12-aryl-and 12-aryl-9,9-dimethyl-8,9,10,12-tetrahydro-7H-benzo[b][4,7]phenanthrolin-11-ones (condensation products of 6-arylmethylene-aminoquinolines with 1,3-cyclohexanedione and dimedone) with sodium nitrite in acetic acid leads to 12-aryl-9,10-dihydro-8H-benzo[b][4,7]phenanthrolin-11-ones. 13-Aryl-7,13-dihydro-12H-indeno-[2,1-b][4,7]phenanthrolin-12-ones obtained by reaction of 6-arylmethyleneaminoquinolines with 1,3-indandione are oxidized to 13-aryl-12H-indeno[2,1-b][4,7]phenanthrolin-12-ones on heating in nitrobenzene.Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 9, 2004, pp. 1369–1375.Original Russian Text Copyright © 2004 by Gusak, Kozlov, Tereshko.     

Dimeric samarium(III) alkoxides bearing N2O2 tetradentate Schiff bases and their utility for the catalytic epoxidation of trans-chalcone

Two anhydrous, dimeric samarium(III) complexes bearing a bulky μ-alkoxide (diphenylmethoxide) ligand and different “saturated” tetradentate Schiff bases {bis-5,5′-(1,3-propanediyldiimino)-2,2-dimethyl-4-hexene-3-onato and bis-5,5′-(2,2-dimethyl-1,3-propanediyldiimino)-2,2-dimethyl-4-hexene-3-onato} were synthesized and fully characterized. The complexes differ only in alkyl substitution at the three-carbon amino linker between the ketoiminato halves, with one having a CH₂ group and the other a C(CH₃)₂ substituent along the free-ligand idealized mirror plane. Both metal-containing molecules were isolated in high-yields from direct alcoholysis of the corresponding 5-coordinate, mononuclear complexes and their catalytic activity for the epoxidation of 1,3-diphenyl propenone (trans-chalcone), an α,β-unsaturated ketone, investigated.     

Synthesis and some heterocyclization reactions of new diethyl (1,1-difluoro-3,3-dicyano-2-trifluoromethylallyl)phosphonate and ethyl 3,3-dicyano-2-[(diethoxyphosphoryl)difluoromethyl]acrylate

A new CF₂X-analogue of 1,1-bis(trifluoromethyl)-2,2-dicyanoethylene (X = P(O)(OEt)₂), diethyl (1,1-difluoro-3,3-dicyano-2-trifluoromethylallyl)phosphonate, has been synthesized from diethoxyphosphoryl pentafluoroacetone 1. A similar phosphoryl analogue of ethyl 3,3-dicyano-2-trifluoromethylacrylate, ethyl 3,3-dicyano-2-[(diethoxyphosphoryl)difluoromethyl]acrylate, has been obtained from ethyl 3-(diethoxyphosphoryl)-3,3-difluoro-2-oxopropionate 2. By heterocyclization of these new ethylenes with 3-methyl-2-pyrazoline-5-ones, 3(5)-aminopyrazoles, dimedone, 2-aminopyridines, 1-aryl-3-methyl-5-aminopyrazoles, 1,3,3-trimethylisoquinolines, as well as by condensation with anilines and ketones, the difluoromethylphosphonate-substituted derivatives of 1,4-dihydropyrano[2,3-c]pyrazole, 4,5-dihydropyrazolo[1,5-a]pyrimidine, 5,6,7,8-tetrahydro-4H-chromene, 2H-pyrido[1,2-a]pyrimidine, 4,7-dihydro-1H-pyrazolo[3,4-b]pyridine, 1,4-dihydropyridine, 4,5,6,7-tetrahydro-1H-[1]pyrindine, 1,4,5,6,7,8-hexahydroquinoline, and 6,7-dihydro-2H-pyrido[2,1-a]isoquinoline have been obtained in one stage.     

New Chiral Diamines of the Dioxolane Series: (+)-(4S,5S)-2,2-Dimethyl-4,5-bis(diphenylaminomethyl)- 1,3-dioxolane and (+)-(4S,5S)-2,2-Dimethyl-4,5-bis(methyl- aminomethyl)-1,3-dioxolane

The reaction of sodium diphenylamide with 2,2-dimethyl-4,5-bis(tosyloxymethyl)-1,3-dioxolane gave (+)-(4S,5S)-2,2-dimethyl-4,5-bis(diphenylaminomethyl)-1,3-dioxolane, which was brought into complex formation with cobalt chloride. Treatment of 2,2-dimethyl-4,5-bis(tosyloxymethyl)-1,3-dioxolane with sodium N-methylanilide resulted in cleavage of the SÄO bond in the p-toluenesulfonate moiety with formation of N-methyl-N-phenyl-p-toluenesulfonamide and 4,5-bis(hydroxymethyl)-2,2-dimethyl-1,3-dioxolane disodium salt. Diethyl (4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-dicarboxylate reacted with methylamine to give the corresponding dicarboxamide which was reduced with lithium aluminum hydride to (4S,5S)-2,2-dimethyl-4,5-bis(methylaminomethyl)-1,3-dioxolane having chiral carbon and nitrogen atoms.     

Di-4(3H)-quinazolinon-2-yl Derivatives from the Diacid Chlorides of Pinic and sym-Homopinic Acids

The corresponding diamides have been synthesized by the interaction of the diacid chlorides of cis-2,2-dimethyl-3-carboxycyclobutaneacetic acid (pinic acid) and cis-2,2-dimethylcyclobutane-1,3-diacetic acid (sym-homopinic acid) with two equivalents of anthranilic acid. Treatment of the diamides with formamide gave 2,2-dimethyl-1-[4(3H)-quinazolinon-2-yl]methyl-3-[4(3H)-quinazolinon-2-yl]cyclobutane and 2,2-dimethyl-1,3-di[4(3H)-quinazolinon-2-ylmethyl]cyclobutane respectively.     

Di-6R,7R1-4(3H)-Oxo-2-quinazolinyl-substituted Cyclobutanes from Pinic and sym-Homopinic Acids

The corresponding diamides were obtained from reaction of cis-3-carboxy-2,2-dimethylcyclobutylacetic acid (pinic acid) and of cis/trans-3-(carboxymethyl)-2,2-dimethylcyclobutylacetic acid (homopinic acid) dichlorides with two equivalents of 5-bromo-, 4-chloro-, and 4,5-dimethoxyanthranilic acids. Treatment of them with formamide leads to the formation of the corresponding 2,2-dimethyl-3-[4(3H)-oxo-2-quinazolinyl]methyl-1-[4(3H)-oxo-2-quinazolinyl]cyclobutanes and 2,2-dimethyl-1,3-di[4(3H)-oxo-2-quinazolinylmethyl]cyclobutanes.     

1, 5, 6, 7-Tetrahydro-2H-[1,4]diazepin-5,7-dione aus Malonimiden und 3-Dimethylamino-2,2-dimethyl-2H-azirin

1, 5, 6, 7-Tetrahydro-2H-[1, 4]diazepin-5, 7-diones from Malonimides and 3-Dimethylamino-2, 2-dimethyl-2H-azirine Reaction of the aminoazirine 1 with malonimides of type 7 in 2-propanol at room temperature leads to the 1,4-diazepine derivatives of type 9 (Scheme 3). The structure of 6, 6-diethyl-3-dimethylamino-2,2-dimethyl-1,5,6, 7-tetrahydro-2H- [1,4] diazepin-5, 7-dione ( 9a ) has been proved by single crystal X-ray analysis (Chapter 4). Reduction of the 7-membered heterocycle 9a with sodium borohydride yields the perhydro-[1,4]diazepin-5, 7-dione 10 , while 9a in ethanol at 60° undergoes a ring contraction to the 4 H-imidazole derivative 11a (Scheme 4): Mechanisms of these two reactions are discussed in comparison with previously reported reactions (Chapter 5).     

Borohydride reduction of acetophenone and esters of dehydrocarboxylic acids in the presence of chiral cobalt(<Emphasis Type="SmallCaps">II</Emphasis>) diamine complexes

The catalytic reduction of acetophenone, methyl α-acetamidocinnamate, and dimethyl itaconate with alcohol-modified sodium borohydride was studied in the presence of complexes CoCl₂·L₂ (L₂ are chiral C ₂-symmetric diamines: (4S,5S)-2,2-dimethyl-4,5-bis(aminomethyl)-1,3-dioxolane, (4S, 5S)-2,2-dimethyl-4,5-bis(methylaminomethyl)-1,3-dioxolane, (4S, 5S)-2,2-dimethyl-4,5-bis(dimethylaminomethyl)-1,3-dioxolane, and (4S, 5S)-2,2-dimethyl-4,5-bis(diphenylaminomethyl)-1,3-dioxolane). The maximum enantiomeric excess of (S)-1-phenylethanol was 24%, that of dimethyl α-methylsuccinate was 38%.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 342–347, February, 2005.     

A hydrogen pump: Transfer of four hydrogens from a cyclohexane ring to a triple bond during a menthofuran/bromoacetylene adduct rearrangement

The cycloadducts of menthofuran with acylbromoacetylenes, (3-bromo-1,6-dimethyl-5,6,7,8-tetrahydro-2H-2,4a-epoxynaphthalen-4-yl)(aryl)methanones, rearrange (CHCl₃, reflux, 1 h) to 2-(2-acylethyl)benzofurans (along with the expected 2-bromo-3-hydroxy-4,7-dimethyl-5,6,7,8-tetrahydronaphthalene-1-yl)(aryl)methanones) via 2-acylethynylmenthofurans, thus indicating the exceptionally mild and rapid transfer of four hydrogens from a cyclohexane ring to a triple bond through the furan moiety in the key intermediate 2-acylethynylmenthofuran.     

ansa-metallocene derivatives: XI. Synthesis and crystal structure of a chiral ansa-titanocene derivative with trimethylene-bridged tetrahydroindenyl ligands

The chiral ansa-titanocene derivative 1,3-propanediylbis(4,5,6,7-tetrahydro-1-indenyl)titanium(IV) dichloride has been prepared by reaction of the dilithium salt of 1,3-bis(indenyl)propane with TiCl₄ and subsequent hydrogenation. The product has been shown by an X-ray diffraction study to be the R,S metal-ring linkage isomer; in this trimethylene-bridged ansa-metallocene the axial symmetry previously observed for te ethylene-bridged congener is destroyed by a non-symmetric location of the (CH₂)₃ bridge.     

2-amino-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidines: Synthesis and reactions with electrophilic reagents

The hydrogenation of 2-amino-5-R-7-R′-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidines with NaBH₄ led to the formation of 2-amino-5-R-7-R′-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]pyrimidines. Acylation, sulfonylation, and alkylation of these compounds depending on conditions and the reagent character occur at the amino group, atoms N³ or N⁴. The treatment with alkali of 2-amino-3-benzyl-5-R-7-R′-4,5,6,7-tetrahydro-1,2,4-triazolo-[1,5-a]pyrimidinium bromide resulted in 2-amino-3-benzyl-5-R-7-R′-3,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]-pyrimidine, similar reaction of 2-acetamido-3-benzyl-5-R-7-R′-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]-pyrimidinium bromide gave a mesoionic product of a hydrogen elimination from the amide nitrogen atom.