Efficient synthesis of 5-alkyl amino and thioether substituted pyrazoles

Nucleophilic substitution reactions of 1-(4-methylsulfonyl-2-pyridyl)-5-chloro pyrazoles with various substitutions at the 4 position with amine nucleophiles and thiols occur under mild conditions to provide the 5-alkyl amino and thioether pyrazoles in high yields.     

Efficient fluoride-mediated synthesis of 5-alkyl amino- and ether-substituted pyrazoles

Fluoride-mediated nucleophilic substitution reactions of 1-(4-methylsulfonyl (or sulfonamido)-2-pyridyl)-5-chloro-4-cyano pyrazoles with various amines and alcohols occur under mild conditions to provide the 5-alkyl amino and ether pyrazoles in moderate to high yields.     

Synthesis of 4-alkyl functionally substituted 7-dialkylaminocoumarins

7-Dialkylaminocoumarins that, depending on the reaction conditions, contain an alkyl substituent with one or two functional groups in the 4 position, were obtained in the reaction of 4-chloro-7-diethylamino-, 4-chloro-7-N-morpholino-, and 2,3,6,7-tetrahydro-9-chloro-1H,5H-quinolizino[9,9a,1-gh]coumarin with sodium derivatives of acetylacetone and acetoacetic, malonic, and cyanoacetic esters. The spectralluminescence characteristics of the synthesized compounds were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1326–1330, October, 1990.     

Solid-phase synthesis of 5-substituted amino pyrazoles

An efficient method for the solid-supported synthesis of 5-N-alkylamino and 5-N-arylamino pyrazoles is described. This method is general and mild and utilizes readily accessible resin-immobilized beta-ketoamides 2 as starting materials for the preparation of 1. Resin-immobilized beta-ketoamide, aryl-, or alkylhydazine and Lawesson's reagent are suspended in a mixture of THF/Py and heated at 50-55 degrees C to give a resin-bound 5-aminopyrazole, that is liberated from the solid support by treatment with TFA.     

Expedient synthesis of pyrazoles substituted with amino, hydroxyl and thioamide groups

The reaction of α,β-acetylenic γ-hydroxy nitriles with thiosemicarbazide, under mild conditions (rt, no catalyst, in 1:1 aqueous ethanol, 4-14 h), proceeds chemo-, regio- and stereoselectively to give atypically so far inaccessible tri-functionalized (amino, hydroxyl and thioamide groups) pyrazoles in 53-91% yields. The hydroxyl function is easily protected by using the corresponding acetals of the starting acetylenic hydroxy nitriles.     

Facile and efficient synthesis of acridinediones from primary amino alcohols via three-component condensation reactions assisted by microwave irradiation

Microwave irradiation of three component reaction of dimedone, appropriate aromatic aldehydes and amino alcohols in a stoichiometrical ratio 2:1:1 for few minutes afforded the formation of a stable fused three membered ring of the corresponding 3,6,6-tetramethyl-2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione derivatives in an excellent yield (80–91%). The structure of all products has been characterized by X-ray crystal structural analyses, ¹³C NMR, ¹H NMR, IR and mass spectrum analyses.     

Facile oxygenation reactions of ruthenium acetylide complex containing substituted olefinic group

Reaction of the ruthenium acetylide complex Cp(dppe)RuC≡CCH(OMe)CPh(2)-CH(2)CH=CMe(2) (5a) with oxygen readily gives acetone and the acyl complex 6 in almost quantitative yield. Protonation of 5a is followed by an elimination of MeOH and a hydroxyl addition at Cα in the presence of water to give the hydroxycarbene complex 7a. The structures of the acyl complex 6 and the hydroxycarbene complex 7c are fully characterized by single crystal X-ray diffraction analysis.     

Cyclocondensation of α-hydroxyimino-β-alkyl/arylimino-β-methylthioketones with hydrazine hydrate: Synthesis of 3(5)-aryl-5(3)-alkyl/arylamino-4-nitroso (or amino) pyrazoles

The title pyrazoles were synthesized through cyclocondensation of hydroxyiminoimine derivatives 1a-j with hydrazine hydrate.     

Reaction of hydrazonyl chlorides and carboalkoxymethylene triphenylphosphoranes to give 5-alkoxy substituted pyrazoles

The reaction of ethyl chloroglyoxylate phenyl hydrazone and diphenyl hydrazonyl chloride with several carboalkoxymethylene triphenylphosphoranes has been examined. The products isolated correspond to N-phenyl-3-carboalkoxy-5-alkoxy substituted pyrazoles. The mechanism advanced to account for the formation of the products involves the stepwise addition of a nitrile imine intermediate with the Wittig reagent.     

Solvent-free synthesis of 4-aryl substituted 5-alkoxycarbonyl-6-methyl-3,4-dihydropyridones under microwave irradiation

4-Aryl substituted 5-alkoxycarbonyl-6-methyl-3,4-dihydropyridones have been prepared in one-pot condensation from Meldrum's acid, methyl acetoacetate and the appropriate benzaldehyde in the presence of ammonium acetate using microwave irradiation without solvent. This rapid method produced pure products in high yields (81-91%) due essentially to a specific non-thermal microwave effect (17-28%) by conventional heating under the same conditions.     

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.     

Ring contraction of a 5-acetylpyrimidine into pyrazoles by the action of substituted hydrazines in acidic medium

We have found previously that two 5-acetyl-4-methylpyrimidines could be transformed by aminoguanidine hydrochloride into 4-acetyl-1-amidino-3-methylpyrazolyl amidinohydrazone dihydrochloride. This reaction beside the fact that it led to a molecule closely related to the antitumor drug M.G.B.G. pointed out to a new possibility of ring contraction of pyrimidines into pyrazoles. We attempted therefore to study the possibility of extending this transformation to other substituted hydrazines and to define more accurately the conditions of this reaction as well as to prepare new potential anticancer drugs.     

Highly regioselective synthesis of 1-aryl-3 (or 5)-alkyl/aryl-5 (or 3)-(N-cycloamino)pyrazoles

[Reaction: see text]. An efficient highly regioselective protocol for the synthesis of isomeric 1,3-diaryl (or 1-aryl-3-alkyl) and 1,5-diaryl (or 1-aryl-5-alkyl)-5 (or 3)-(N-cycloamino)pyrazoles has been reported by cyclocondensation of common alpha-oxoketene N,S-acetal precursors with arylhydrazines by variation of reaction conditions.     

Synthesis of 4-formyl estrone using a positional protecting group and its conversion to other C-4-substituted estrogens

4-Formyl estrone was synthesized in overall good yield in three steps starting from estrone. This was achieved by conducting an electrophilic aromatic substitution reaction using formaldehyde, triethylamine, and MgCl2 on 2-tert-butyl estrone, which was readily prepared in 96% yield from estrone using tert-butyl alcohol and BF3OEt2. The tert-butyl group acted as a positional protecting group to prevent reaction at the 2-position. The tert-butyl group was readily removed in good yield using AlCl3 in dichloromethane/CH3NO2. To our knowledge, this represents the first use of a positional protecting group for the synthesis of a C-4-modified estrogen. 4-Formyl estrone was used as a common precursor to obtain a variety of other C-4 modified estrogens in very high yields such as 4-methylestrone and 4-hydroxymethylestrone as well as the novel estrogen 4-carboxyestrone. The syntheses of 4-formyl, -methyl-, and -hydroxymethyl estrone represent dramatic improvements over previously reported syntheses of these compounds.     

Facile synthesis of 2-(substituted amino)-4H-thieno[3,2-e]-1,3-thiazin-4-ones

Interaction between 2,5-dichlorothiophene-3-carbonyl isothiocyanate, accessible via 2,5-dichlorothiophene-3-carbonyl chloride, and model heterocyclic amines produced the respective 2,5-dichloro-N-(substituted aminocarbonothioyl)thiophene-3-carboxamides. Upon heating, the deprotonated form of the latter underwent intramolecular cyclization to deliver the corresponding 2-(substituted amino)-4H-thieno[3,2-e]-1,3-thiazin-4-ones. The structures of these new bicyclic derivatives and their acyclic precursors are based on microanalytical and spectral (IR, MS, and NMR) data.     

Convenient replacement of the hydroxy by an amino group in 4 hydroxycoumarin and 4-hydroxy-6-methyl-2-pyrone under microwave irradiation

The reaction of 4-hydroxycoumarin (1) with some primary amines 2a-h and morpholine (2i) under microwave irradiation occurred without opening of the lactone ring to give N-substituted 4-aminocoumarins 3a-i in excellent yields. Under the same experimental conditions, 4-hydroxy-6-methyl-2-pyrone (4) reacted with benzylamine (2e) or 2-phenyl- ethylamine (2f) to give the corresponding N,N'-disubstituted 4-amino-6-methyl-2-pyridones 5e,f. The main advantages of this procedure are dramatically shortened reaction times, higher amine utilization and considerably improved yields.     

Simple preparations of 4 and 5-iodinated pyrazoles as useful building blocks

The pyrazole nucleus has recently become a recurrent scaffold in the research fields of CropScience and oncology. We report here the preparation of an array of 4- and 5-iodinated pyrazole derivatives, such as 4-iodo-3-trifluoromethylpyrazole or ethyl 5-iodo-4-carboxy-3-trifluoromethylpyrazoles. This work provide access to many new pyrazole derivative, including 11 original out of 16 iodinated building blocks, thus opening accesses to new chemical entities featuring a pyrazole nucleus.     

Contrasting chemoselectivities in the ultrasound and microwave assisted bromination reactions of substituted alkylaromatics with N-bromosuccinimide

Ultrasound and microwave assisted bromination reactions of various alkylaryls with N-bromosuccinimide, either neat or in water, shows diverse chemoselectivity. Thus, ring substitution occurs in water with ultrasound, whereas with microwaves both side-chain α-bromination and ring substitution occur. With neat reactants, side-chain α-bromination predominates for microwave assisted reactions. In the presence of water the chemoselectivity with microwave-promoted bromination is similar to that observed using classical methods.     

Facile and efficient synthesis of quinoline-4-carboxylic acids under microwave irradiation

<正>A facile and efficient method for the preparation of 2-non-substituted quinoline-4-carboxylic acids is described via the Pfitzinger reaction of isatins with sodium pyruvate following consequent decarboxylation under microwave irradiation.