Modification of biologically active amides and amines with fluorine-containing heterocycles 1. Novel fluorine-containing heterocyclic derivatives of streptocide

Three-component reaction of Piracetam, methyl trifluoropyruvate and 1,3-binucleophiles, such as 6-aminouracils, 6-aminothiouracils, 4-(4-tolylamino)pent-3-en-2-one and N-substituted ureas, has been studied. This reaction resulted in fluorinated heterocyclic derivatives of Piracetam.     

A Novel Synthesis of N-Aryl-6-methylsulfanyl-4-pyrimidinones and Purine Analogues: The Reaction of Dimethyl N-Cyanodithioiminocarbonate with Cyanoacetanilides

Abstract

A novel and efficient method for the synthesis of N-aryl-6-methylsulfanyl-4-oxopyrimidine-5-carbonitriles via the reaction of dimethyl N-cyanodithioiminocarbonate with substituted cyanoacetanilides has been investigated. (3)N-Aryl-2,5-diamino-7H-pyrazolo[3,4-d]-pyrimidin-4(3H)-one have also been prepared from the reaction of 6-sulfanylthio-N-aryl-4-pyrimidinones with hydrazines.     

Facile Synthesis of Nicotinic Acid Derivatives with Unsymmetrical Substitution Patterns

Abstract

Two novel methods for synthesis of nicotinic acid derivatives with unsymmetrical substitution patterns were presented via ketene dithioacetals. The ketene N,S-acetals 2 reacted with β-ketoesters or β-cyanoesters to give 4-amino-5-cyano-2-alkyl-6-methylthio-nicotinic acid derivatives 3 or 2,4-diamino-5-cyano-6-methylthio-nicotinic acid ethyl ester 4. However, 6-amino-5-cyano-2-alkyl-4-methylthio-nicotinic acid esters 6 were obtained by the reaction of the ketene dithioacetals 1 and β-amino-crotonates.     

Synthesis and structure of new 2,4-dicyano-6-oxo-3-phenylbicyclo[3.2.1]octane-2,4-dicarboxylates

The sequential reaction of furfural with cyclic secondary amines and further with benzaldehyde and cyanoacetates affords new 2,4-dicyano-8-(R₂N)-6-oxo-3-phenylbicyclo[3.2.1]-octane-2,4-dicarboxylates as rac-(1R,2R,3R,4S,5S,8R)-diastereomers. The structures of the reaction products were determined by X-ray diffraction.

     

Synthesis and properties of substituted 2-thioxohexahydropyrimidine-5-carbohydrazides

A regioselective method for the synthesis of substituted (4R*,5S*,6R*)-2-thioxohexahydro-pyrimidine-5-carbohydrazides from the corresponding diastereomers of hexahydro-2H-chromeno[4,3-d]pyrimidines was developed. In acidic medium, the obtained hydrazides are prone to retro reaction to give hexahydro-2H-chromeno[4,3-d]pyrimidines.

     

A new route to the synthesis of 4-amino-substituted pyrido[2,3-d]pyrimidin-5-one derivatives

The reaction of 6-(R-amino)-5-acetyl-4-methylsulfonyl-2-phenylpyrimidines with amines was studied. 6-Arylamino derivatives react with alkylamines to form 6-alkylamino-4-arylamino-5-acetyl-2-phenylpyrimidines, which upon refluxing in benzene with dimethylformamide dimethylacetal are converted to 4-alkylamino-8-aryl-2-phenylpyrido[2,3-d]pyrimidin-5(8H)-ones. The cyclization proceeds selectively with participation of the arylamino group only, the alkylamino group being not involved. At the same time, refluxing of 5-acetyl-4,6-dibenzylamino-2-phenylpyrimidine with dimethylformamide dimethylacetal in toluene affords the product of condensation on the acetyl group, which upon refluxing in o-xylene transforms to 4-benzylamino-8-benzyl-2-phenylpyrido[2,3-d]pyrimidin-5(8H)-one.

     

Ecofriendly and highly efficient microwave-induced synthesis of novel quinazolinone-undecyl hybrids with in vitro antitumor activity

Abstract

Novel N-alkyl-quinazolin-4-one derivatives 3–5 were obtained from reaction of 6-Iodo-2-undecylquinazolin-4(3H)-one (2) with different alkyl halides. Hydrazinolysis of compound 5 gave the acetohydrazide 6 which reacted with different carbon electrophiles to produce 2-undecyl-4(3H)-quinazolinone derivatives. The new products were obtained by either conventional method or by microwave assisting technique and the structure of all products was confirmed by elemental and spectral data. The ecofriendly microwave provides an efficiency over than conventional method in many aspects. All the synthesized products were tested in vitro against a panel of three human tumor cell lines, namely, hepatocellular carcinoma (liver) HepG2, colon cancer HCT-116, and mammary gland breast MCF-7. Almost all of the tested compounds showed satisfactory activity.     

Intramolecular 6-endo-dig-Cyclization of Ethyl 5-Aminomethyl-4-(1,2,3-thiadiazol-4-yl)furan-2-carboxylate

The reaction of 5-aminomethyl-4-(1,2,3-thiadiazol-4-yl)furan-2-carboxylic acid ethyl ester with bases has given ethyl 5-sulfanylidene-4,5,6,7-tetrahydrofuro[2,3-c]pyridine-2-carboxylate as a result of intramolecular 6-endo-dig-cyclization of thioketene generated in situ with an internal CH₂NH₂ nucleophile. The obtained ester has been alkylated with iodomethane at the sulfur atom to form ethyl 5-methylsulfanyl-4,7-dihydrofuro[2,3-c] pyridine-2-carboxylate. The Hantzsch reaction with ω-bromoacetophenone has resulted in the formation of 7-ethoxycarbonyl-3-phenylfuro[3,2-d[1,3]thiazolo[3,2-a]pyridin-4-ium bromide.

     

Thiophosphorylation of Pharmacophoric Phenols,Diols, and Triols

Abstract

Novel organyldithiophosphonic and bis(aryldithiophosphonic) acids were obtained by the reaction of 2,4-diorganyl 1,3,2,4-dithiadiphosphetane-2,4-disulfides with paracetamol, 4-(1H-pyrrol-1-yl)phenol, ethambutol dihydrochloride, vitamin B₆, and its acetonide derivatives.     

Catalytic Cycloaminomethylation of Aminobenzamides with 1,3-Bis[dimethylamino(methoxy)methyl]thiourea

Efficient methods of the synthesis of cyclophanes containing the thiourea moiety via the reaction of o-, m-, and p-aminobenzamides with 1,3-bis(dimethylaminomethyl)thiourea or 1,3-bis(methoxymethyl)thiourea using NiCl₂·6H₂O and SmCl₃·6H₂O as catalysts have been developed.

     

Reactions of 3-(Polyfluoroalkyl)propane-1,2,3-trione-2-oximes with Diaminoarenes

Novel quinoxaline derivatives have been synthesized via the reaction of 3-trifhioromethyl-1,2,3-propanetrione-2-oximes with 1,2-diaminobenzene or 2,3-diaminonaphthalene: 2-trifluoromethyl-3-aroylquinoxaline and 2-trifluoromethyl-3-aroylbenzo[g]quinoxaline. Under similar conditions, 3-R^F-1,2,3-propanetrione-2-oximes [R^F = C₃F₇, H(CF₂)₄, C₄F₉, and C₆F₁₃] with the same diaminoarenes have given a mixture of the condensation and fragmentation products in different ratios. The structure of (4-methylphenyl)[3-(tri-fluoromethyl)benzo[g]quinoxalin-2-yl]methanone has been elucidated by means of X-ray diffraction analysis.

     

Efficient Synthesis and Fungicidal Activities of 2-Alkylthiobenzofuro[3,2-d]Pyrimidinones

2-Alkylthiobenzofuro[3,2-d]pyrimidinones 5 and 6 were synthesized by S-alkylation of 2,3-dihydro-2-thioxobenzofuro[3,2-d]pyrimidin-4(1H)-ones 4, which were obtained via aza-Wittig reaction of iminophosphorane 2 with CS₂ and further reaction of the product with various amines. Compounds 5 and 6 exhibited fungicidal activity. For example, compound 6a, which has a small N-substituted methyl group, showed the best inhibitive activity (91%) against Dothiorella gregaria at 50 mg/L.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

(NH4)6Mo7O24·4H2O as an Efficient,Selective, and Reusable Catalyst for the Oxidation of Thiols to Disulfides Using Potassium Bromate

Abstract

Ammonium molybdate, (NH₄)₆Mo₇O₂₄·4H₂O, is found to be an efficient and selective catalyst for the oxidation of thiols to corresponding disulfides using potassium bromate in aqueous acetonitrile as the solvent. Among various solvents tested, CH₃CN/H₂O showed better results in terms of the reaction yield and rate. In the absence of (NH₄)₆Mo₇O₂₄·4H₂O, the oxidation reaction is not selective for the formation of disulfides. The catalyst can be easily recovered after completion of the reaction and reused without any significant loss of its activity.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional text and figures.]     

A Convenient Synthesis of 2, 3 - DI- O - Acetyl-1, 6 - Anhydro- β - D – Glucopyranose

Abstract

1, 2, 3-Tri-O-acetyl-6-O-benzyl-4-O-chloroacetyl-α- and -β-D-glucopyranose (4α β)were derived from 1, 2, 3-tri-O-acetyl-4, 6- O -benzyl-idehe-β-D-giucopyranose (1) in two steps. Compound 1, 1, 2, 3-tri-O -acetyl-β-D-glucopyranose (2), and 4α,β were subjected to the cyclization reaction using Lewis acids ( SnCl₄ and BF₃-etherate), to give corresponding 1, 6-anhydro derivatives.     

Assembling of Thiazolo[3,2-a]pyridinium Salts via the Reaction of 2-Pyridinesulfenyl Halides with Vinyl Ethyl Ether

The regio- and stereoselective synthesis of 3-ethoxy-2H,3H-[1,3]thiazolo[3,2-a]pyridin-4-ium halides via the reaction of 2-pyridinesulfenyl halides with vinyl ethyl ether has been elaborated.

     

A Convenient Synthesis of 1-Amino-4-methyl-4H-3-thia-4,5a,10-triazacyclopenta[a]fluoren-5-ones and Some New 2,3-Dihydro-1,3,4-thiadiazoles

1-amino-4-methyl-4H-3-thia-4,5a,10-triazacyclopenta-[a]fluoren-5-one and 6-methyl-6H-,9H-thia-4b,6,9,11,12-pentaazaindeno[1,2-a]-fluorene-5,8-dione derivatives were prepared from 2-methyl-1-oxo-3-thioxo-2,4,9b-trihydropyrimidino[1,6-a] benzimidazole-4-carbonitrile. Also, 2,3-dihydro-1,3,4-thidazoles were synthesized via a reaction of hydrazonoyl chlorides with 3-(methylamino)-2-substituted 3-thioxopropanenitrile. Structures of newly synthesized compounds were elucidated on the basis of elemental analyses, spectral data, and alternative methods synthesis whenever possible.     

Zum Substitutionsverhalten von Imidazolidin-4-thionen

The reaction of imidazolidine-4-thiones [1, 6 (R=H)] with acyl chlorides and arylsulfonyl chlorides under various conditions to 3-acyl-imidazolidin-4-thiones and 3-arylsulfonyl-imidazolidin-4-thiones are described. 3-Alkyl-imidazolidine-4-thiones are synthesized in the same way. 1-Phenylcarbamoyl-imidazolidine-4-thiones (8, 9) are obtained by reacting1 and6 (R=H) with phenyl isocyanate. By oxidation with KMnO₄ in absol. acetone2 (R=COC₅H₁₁) is converted into 3-hexanoyl-2,2,5,5-tetramethyl-imidazolidine-4-one (10).

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Herrn Dr. phil.Günther W. Ibing zum 65. Geburtstag gewidmet.

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89. Mitt.:F. Asinger, A. Saus, E. Fichtner undW. Leuchtenberger, Mh. Chem.106, 1461 (1975).

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K. Hentschel, Teil der Dissertation, Technische Hochschule Aachen, Inst. f. Techn. Chem. u. Petrolchemie, 1974.     

Hydroxyalkylation of α-Phosphonylated α-Silylated Allylic Carbanions. An Unexpected Cyclization Reaction

Abstract

When reacted with aldehydes, in situ generated title carbanions 2 can give phosphonodienes (4 or 6), phosphonolactones (5 or 8) or phosphonoalcohols 7, depending on structure of reagents and on reaction conditions.     

Deep eutectic solvent-mediated expedient multicomponent synthesis of oxazine scaffolds

A simple, efficient, and eco-friendly protocol for the synthesis of 1,3-oxazine derivatives, viz. 7-aryl-7,8-dihydro-6H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-e][1,3]oxazines and 3-aryl-3,4-dihydro-2H- naphtho[2,3-e][1,3]oxazine-5,10-diones, involving one-pot multicomponent condensation reaction of various amines and formaldehyde with sesamol/2-hydroxy-1,4-naphthoquinone, respectively, catalyzed by a choline chloride–oxalic acid deep eutectic solvent has been developed. The method offers several advantages, including mild reaction conditions, simple operating procedure, recyclable and biodegradable catalyst, short reaction times, and excellent yields of the target products.

     

Prins-Reaktionen mit Arylaldehyden, 3. Mitt.

By reaction of excess benzaldehyde with cyclohexene in presence of sulfuric acid besider-2,c-4-diphenyl-(t-4aH,c-8aH)-hexahydro-4H-1,3-benzodioxin (2) andr-4-phenyl-(t-4aH,c-8aH)-hexahydro-4H-1,3,2-benzodioxathiin-2,2-dioxide (3),trans-2-benzyloxycyclohexyl phenyl ketone (5) and (E)-3-benzylidene-1-cyclohexenyl phenyl ketone (6) are obtained. The formation of5 and6 is shown to proceed via an acid catalyzedCannizzaro reaction of benzaldehyde.

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2. Mitt.:H. Griengl undK. P. Geppert, Mh. Chem.107, 675 (1976).