A novel one-pot synthesis of some new interesting pyrrole derivatives

[reaction: see text] 11-(1H-Pyrrol-1-yl)-11H-indeno[1,2-b]quinoxaline and 3-(1H-pyrrol-1-yl)indolin-2-one derivatives have been synthesized in good yields in a novel, one-pot, and efficient process by condensation of 11H-indeno[1,2-b]quinoxalin-11-one or isatin derivatives with 4-hydroxyproline on solid-support montmorillonite K10 under microwave irradiation.     

Unusual reaction of 2-(trifluoromethyl)-1,2-dihydro-3lambda(6)-thieno- [2,3-c]chromen-3,3,4-triones with hydrazine as a new route to 3-hydrazinopyridazine derivatives

Oxidation of 2-(trifluoromethyl)-1,2-dihydro-4H-thieno[2,3-c]chromen-4-ones 2 with H(2)O(2) in AcOH gives 2-(trifluoromethyl)-1,2-dihydrothieno[2,3-c]chromen-3,3,4-triones 3, which are transformed into 3-hydrazinopyridazine derivatives 4 in high yields by treatment with hydrazine hydrate in ethanol.     

The formation of the indolizino[1,2-c]quinolinium system by a novel nucleophilic reaction

2-Methyl-3-(2-pyridyl)quinoline (1) with a bromomethyl ketone or ethyl bromoacetate yields 6-methyl-12-acylindolizino[1,2-c]quinolinium bromides ( 5–9 ). The acyl derivatives can be deacylated in acid yielding 6-methyl indolizino[1,2-c]quinolinium salts ( 4 ). Benzoylation of 4 yields the 12-benzoyl derivative ( 6 ). The deacylation product ( 4 ) has been synthesized from 2-acetamidophenacyl bromide ( 10 ) and 2-pyridylacetone ( 12 ).     

New nucleoside analogs from 2-amino-9-(beta-D-ribofuranosyl)purine

Four novel derivatives of 2-amino-9-(beta-D-ribofuranosyl)purine (1) were synthesised and fully characterised. When 1 was reacted with chloroacetaldehyde (a), 2-chloropropanal (b), bromomalonaldehyde (c) and a mixture of chloroacetaldehyde + malonaldehyde (d), 3-(beta-D-ribofuranosyl)-imidazo-[1,2a]purine (2), 3-(beta-D-ribofuranosyl)-5-methylimidazo-[1,2a]purine (3), 3-(beta-D-ribofuranosyl)-5-formylimidazo-[1,2a]purine (4) and 9-(beta-D-ribofuranosyl)-2-(3,5-diformyl-4-methyl-1,4-dihydro-1-pyridyl)purine (5) were formed, respectively. The products were isolated, purified by chromatography and characterised by MS, complete NMR assignment as well as fluorescence and UV spectroscopy. The yields of these reactions were moderate (14-20%). The fluorescence properties differed from those of the starting compound and the quantum yields were considerably lower.     

A Convenient Synthesis of 2-Arylnaphtho[1,2-d]oxazole Derivatives Promoted by Triethylamine

A variety of 2-arylnaphtho[ 1,2-d]oxazole derivatives were efficiently synthesized in moderate to high yields by the reaction of aromatic aldehydes with 1-amino-2-naphthol derivatives in the presence of triethylamine in refluxing ethanol in air. Seven new 2-arylnaphtho[1,2-d]oxazole derivatives were obtained and characterized by the spectral data and elemental analysis. In addition, the X-ray crystal structures of 2-[4-（N,N-dimethylamino）phenyl]naphtho[ 1,2-d] oxzole （3d） and 1, 1＇-bis（naphtho[ 1,2-d]oxazol-2-yl）ferrocene （3n） have been determined.     

Reaction of β-lactam carbenes with 2-pyridyl isonitriles: a one-pot synthesis of 2-carbonyl-3-(pyridylamino)imidazo[1,2-a]pyridines useful as fluorescent probes for mercury ion

The one-pot reaction of β-lactam carbenes with 2-pyridyl isonitriles followed by an acidic hydrolysis was reported, which produced 2-carbonyl-3-(pyridylamino)imidazo[1,2-a]pyridines in moderate to good yields. Among the resulting novel imidazo[1,2-a]pyridine derivatives, 1-(6-chloro-3-(5-chloropyridin-2-ylamino)imidazo[1,2-a]pyridin-2-yl)-2-ethylbutan-1-one was demonstrated to be an efficient fluorescent probe for mercury ion both in acetonitrile and in buffered aqueous solution.     

Solvent-dependent reactions for the synthesis of β-keto-benzo-δ-sultone scaffolds via DBU-catalyzed O-sulfonylation/intramolecular Baylis-Hillman/1,3-H shift or dehydration tandem sequences

We have developed a solvent-dependent method for the synthesis of novel benzo-δ-sultone scaffolds. A variety of benzylbenzo[e][1,2]oxathiin-4(3H)-one-2,2-dioxides were obtained in high yields in DMF using a one-pot, DBU-catalyzed condensation of 2-hydroxybenzaldehydes with a number of (E)-2-phenylethenesulfonyl chlorides. On the other hand, the initially prepared 2-formylphenyl-(E)-2-phenylethenesulfonate derivatives underwent DBU-catalyzed reactions to a series of 3-[methoxy(phenyl)methyl]benzo[e][1,2]oxathiine-2,2-dioxides in moderate to good yields in MeOH. These reactions presumably proceed via DBU-catalyzed O-sulfonylation/intramolecular Baylis-Hillman/1,3-H shift or dehydration tandem sequences, respectively.     

Facile and Green Method for the Synthesis of β-Aminoketone Derivatives in Aqueous Media

Three-component reaction of aromatic aldehyde, 2-naphthalenamine, and 1,2-diphenylethanone in aqueous media catalyzed by triethylbenzylammonium chloride (TEBAC) at 90 °C gave 3-aryl-3-(naphthalen-2-ylamino)-1,2-diphenylpropan-1-one derivatives. The enol form of 1,2-diphenylethanone was tentatively proposed to participate in the formation of the products. Compared with previous methods, this three-component reaction has the advantages of green solvent, good yields, and operational simplicity.     

Alkoxide-induced reactions of N-substituted saccharins. Synthesis of 1,2-benzothiazocine 1,1-dioxide and 2,3-dihydropyrrolo[1,2-b]-[1,2]benzisothiazole 5,5-dioxide derivatives

The reactions of saccharin derivatives 1 with sodium alkoxides were studied. Under mild conditions, compounds 1a-f gave the corresponding open sulfonamides 5a-f . Under drastic conditions, β-(saccharin-2)propionic acid derivatives 1a,b reacted with sodium ethoxide affording saccharin and β-ethoxypropionic acid derivatives 4a,b . γ-(Saccharin-2)butyric acid derivatives 1c,d and γ-(saccharin-2)-butyrophenone 1f reacted with sodium t-butoxide in dimethyl sulfoxide affording 5-substituted 6-hydroxy-3,4-dihydro-2H-1,2-benzothiazocine 1,1-dioxides 9 . From mother liquors, 1-substituted 2,3-dihydro-pyrrolo[1,2-b][1,2]benzisothiazole 5,5-dioxides 10 were isolated several hours later, though not detected immediately after completing the reaction. When the reactions were carried out in t-butyl alcohol, the yields of 9 diminished and those of 10 increased with product ratio inversion. Different experimental observations on the possible pathway generating 9 and 10 are discussed.     

A highly regio- and stereoselective nickel-catalyzed ring-opening reaction of alkyl- and allylzirconium reagents to 7-oxabenzonorbornadienes

[Reaction: see text]. An efficient method for the synthesis of cis-2-alkyl- or allyl-1,2-dihydronaphthalenes via a nickel-catalyzed highly regio- and stereoselective ring-opening addition of alkyl- or allylzirconium reagents to 7-oxabenzonorbornadienes is described. Treatment of 7-oxabenzonorbornadienes 1a-c with various alkylzirconium reagents 2a-j (Cp2ZrClCH2CH2R: R = tert-butyl, n-butyl, n-pentyl, -(CH2)3CH=C(CH3)2, -SiMe3, -CH2SiMe3, -(CH2)3Br, cyclopentyl, cyclohexyl, and benzyl) in the presence of NiBr2(dppe) and Zn powder in dry THF at 50 degrees C afforded the corresponding cis-2-alkyl-1,2-dihydronaphthalene derivatives 3a-m in good yields. In addition, allyl zirconium reagents 4a-c also underwent ring-opening reactions with 1a and 1c to give 5a-d in very good yields. The alkylative ring-opening products from 7-oxabenzonorbornadiene can be further converted to naphthalene derivatives 6a-c, via an acid-mediated dehydration, in good to excellent yields. A possible mechanism for the present catalytic reaction was proposed.     

Parallel solid-phase synthesis of 2-imino-4-oxo-1,3,5-triazino[1,2-a]benzimidazoles via tandem aza-Wittig/heterocumulene-mediated annulation reaction

The parallel synthesis of a large number of 2-imino-4-oxo-1,3,5-triazino[1,2-a]benzimidazole derivatives via a solid-phase 1,3,5-triazino-annulation reaction is described. The solid-phase approach involves the in situ generation of iminophosphorane derivatives derived from resin-bound 2-aminobenzimidazoles employing Mitsunobu conditions. The subsequent Aza-Wittig reaction of the iminophosphoranes with isocyanates leads to highly reactive carbodiimides, which undergo an intramolecular heterocyclization reaction to form tetrasubstituted 2-imino-4-oxo-1,3,5-triazino[1,2-a]benzimidazoles in high yields (74-94%) and good purity (>80%).     

Attempts to prepare some 3-substituted azolo[1,2-x]azines,intermediates in the synthesis of azaaplysinopsin derivatives

Some 3-substituted pyrrolo[1,2-a]azines 4a-d were prepared in low yields from the corresponding 2-methylpyridines 1a,b and pyrazine derivatives 1c,d by quaternization with methyl bromoacetate followed by treatment with N,N-dimethylformamide dimethyl acetal. Ethyl 2-pyridinylacetate ( 5 ) and 2-pyridinylaceto-nitrile ( 6 ) were converted with 4-(2-bromo-1-dimethylaminoethylidene)-2-phenyl-5(4H)-oxazolone ( 9 ) into pyrrolo[1,2-a]pyridine derivatives 10 and 12 , intermediates in the synthesis of azaaplysinopsins.     

New route to 3-alkylthiazolo[3,2-a]benzimidazole derivatives

3-Alkyl-thiazolo[3,2-a]benzimidazole derivatives are obtained in high yields via the corresponding 4-alkyl-N-3-(2-aminophenyl)-thiazoline-2-thiones which are easily prepared from 1,2-diaminobenzene, CS(2) and halogenoketones. This new route compares advantageously with the classical mercaptobenzimidazole routes in term of simplicity,isolated yields and availability of the starting materials.     

Synthesis of C 2-Symmetric Chiral Amino Alcohols: Their Usage as Organocatalysts for Enantioselective Opening of Epoxide Ring

A series of β-amino alcohols derivatives were synthesized from (R)-2-amino-1-butanol and (S)-1,2-propanediol, and they have been used as organocatalaysts in the racemic ring opening of epoxide in good yields with high enantiomeric excess (up to 97%).     

Bis(oxazoline) Lewis acid catalyzed aldol reactions of pyridine N-oxide aldehydes--synthesis of optically active 2-(1-hydroxyalkyl)pyridine derivatives: development, scope, and total synthesis of an indolizine alkaloid

A new, short, and simplified procedure for the synthesis of optically active pyridine derivatives from pro-chiral pyridine-N-oxides is presented. The catalytic and asymmetric Mukaiyama aldol reaction between ketene silyl acetals and 1-oxypyridine-2-carbaldehyde derivatives catalyzed by chiral copper(II)-bis(oxazoline) complexes gave optically active 2-(hydroxyalkyl)- and 2-(anti-1,2-dihydroxyalkyl)pyridine derivatives in good yields and diastereoselectivities, and in excellent enantioselectivities-up to 99 % enantiomeric excess. As a synthetic application of the developed method, a full account for the asymmetric total synthesis of a nonnatural indolizine alkaloid is provided.     

Halophilic reaction of N-sodium-substituted azoles with polyhaloperfluoroethanes containing different vicinal halogen atoms

The reactions of N-sodium-substituted azoles with 2-chloro-1-iodo- tetrafluoroethane, 1,2-dichloro-1-iodotrifluoroethane, and 1,2-dibromo-1-chlorotrifluoroethane have been investigated. As shown for iodo derivatives, it is the chlorine rather than the iodine atom that is substituted by the heterocyclic residue, which is consistent with the halophilic reaction mechanism. In the case of indole, the products of simultaneous N-iodopolyfluoroalkylation and ring-iodination have been isolated. The reaction with 1,2-dibromo-1-chlorotrifluoroetane yields N-(2-bromo-2-chlorotrifluoroethyl)azoles accompanied by minor amounts of N-(2,2-dibromotrifluoroethyl) derivatives as by-products.     

Access to new 2-oxofuro[2,3-b]pyrroles and 2-methylenepyrroles through the reaction of 1,2-diaza-1,3-butadienes and gamma-ketoesters

New and interesting 2-oxofuro[2,3-b]pyrroles and 19-methyl-15-oxa-20-azatricyclo[12.3.3.0(1,14)]icos-18-en-18-carboxylates have been obtained in good yields by the one-pot reaction, in basic medium, of 1,2-diaza-1,3-butadienes with diethyl or dimethyl acetylsuccinate or methyl 2-(1,3-dioxo-2-cyclotetradecyl)acetate, respectively, under mild conditions. Treatment of the same starting materials with diethyl 2-acetylglutarate, in acidic medium, afforded unknown 2-methylenepyrrole derivatives in high yields. Novel 4-(3-oxopropyl)-2,5-dimethyl-1H-pyrrole-3-carboxylates also have been achieved by reacting 1,2-diaza-1,3-butadienes with ethyl or methyl 4-acetyl-5-oxo-hexanoate.     

Greener synthesis using hydrogen peroxide in ethyl acetate of alicyclic ring-fused benzimidazoles and anti-tumour benzimidazolequinones

Environmentally-friendly and cost effective hydrogen peroxide in ethyl acetate was used to prepare in high yields pyrrolo[1,2-a]benzimidazoles from commercial o-(pyrrolidin-1-yl)anilines without the requirement for organic-aqueous extraction and chromatography. Six, seven and eight membered ring-fused analogues were similarly obtained in high yields with methanesulfonic acid required for the pyrido[1,2-a]benzimidazole. Anti-tumour benzimidazolequinone derivatives were obtained in high yield via the cyclization of 3,6-dimethoxy-2-(cycloamino)anilines.     

Synthesis of enantiomerically pure anti-1,2-diaryl and syn-1,2-alkylaryl vic-selenoamines

Phenylselenyl benzylcarbanion stabilized by an (S)-2-p-tolylsulfinyl group evolves in a highly stereoselective way in the reactions with (S)-N-(p-tolylsulfinyl)imines at -98 °C affording diastereomerically pure 1,2-selenoamino derivatives in good yields. The syn or anti relationship of the obtained compounds depends on the alkyl or aryl character of the imine. They are easily transformed into enantiomerically pure (1R,2S)-1-aryl[or (1S,2S)-1-alkyl]-2-(phenylseleno)-2-phenylethylamines by reaction with t-BuLi and subsequent methanolysis of the generated sulfinamide derivatives with TFA.     

An efficient synthesis of 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles

Ethyl α-(dimethylaminomethylene)-2-cyanomethyl-4-phenylquinoline-3-carboxylate(2) as new synthons directed to 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles was obtained by the condensation of ethyl 2-cyanomethyl-4-phenylquinoline-3-carboxylate(1) and N,N-dimethylformamide dimethyl acetal(DMFDMA).Reaction of this enamine with primary amines(3) in HOAc-DMF at120 ℃then affords 2-substituted 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitrile derivatives(4) in good yields by a tandem addition-elimination-cyclization reaction.