Facile synthesis of some new functionalized 2-selenoxopyrimidines

Abstract

Some new functionalized 2-selenoxodihydropyrimidines 1–6 were synthesized in good yields via a simple one-pot reaction. The simple method depended on the reaction of selenourea with some nitrile active methylene compounds under basic-catalyzed conditions. Also, treatment of selenourea with each of malononitrile and ethyl cyanoacetate in the presence of benzaldehyde under the same basic reaction conditions afforded the 2-selenoxopyrimidine-5-carbonitriles 7 and 8, respectively. Furthermore, selenourea reacted with benzaldehyde and different β-dicarbonyl compounds under Biginelli reaction conditions to afford the 2-selenoxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates 10, 11 and 13. Using acetylacetone as a substrate in Biginelli reaction yielded the unexpected 5-benzylidene-4,6-dimethyl-pyrimidine-2(5H)-selenone (14). The structures of the synthesized compounds were established on the basis of elemental analysis, IR, ¹H- and ¹³C-NMR and mass spectral data.     

HYDROCHLORINATION OF 2,3-ACETYLENIC ACIDS WITH THIONYL CHLORIDE IN DIMETHYLFORMAMIDE

ABSTRACT

The reaction of 2,3-acetylenic acids (1a–d) with thionyl chloride in DMF under mild conditions gave E,Z-3-chloro-2-alkenoic acids (2a–d) or esters (3a–d) depending on treating the reaction mixture with either water or alcohols.     

Ultrasound-assisted one pot synthesis of polysubstituted meta-terphenyls using ring transformation strategy

An ultrasound-assisted rapid synthesis of meta-terphenyls 9 by the carbanion-induced ring transformation reaction of 6-aryl-5-methyl-2H-pyran-2-ones 7 with functionalized ketones 8 under basic conditions at room temperature has been delineated. The present method gives an easy access to functionally crowded m-terphenyls 9 with notable features including mild reaction condition, remarkable functional groups tolerance, shorter reaction time and high product yields.     

Synthesis of Some Bicyclic Thiazolo- and Oxothiazolo-Pyrimidines

Abstract

Oxothiazolopyrimidine compounds 2(a–e) were synthesized under reflux condition by a simple one-pot condensation reaction of the pyrimidine derivative 1 and chloroacetylchloride in the presence of silver acetate as a catalyst. In a similar way the thiazolopyrimidine 3 and oxothiazolopyrimidine 4 were synthesized by reaction of pyrimidine derivative 1 with 1,2-dibromoethane and 2-bromopropanoic acid respectively. The yields of products following recrystallization from ethanol were of the order of 55–89%.      

Organic-salt-mediated highly regioselective N3-alkylation of 2-thiophenytoin via Michael reaction under solvent-free conditions

A regioselective N3-alkylation of 5,5-diphenyl-2-thiohydantoin (2-thiophenytoin) using a very efficient mild base K₂CO₃ and α,β-unsaturated esters in the presence of organic salt TBAB (tetrabutylammonium bromide) at room temperature has been reported (3b–3h). The selectivity of this reaction is excellent and products have been produced in good yields under solvent-free conditions. The increase of the reaction temperature to 70°C mostly disappeared this selectivity and afforded only the N1,N3-dialkylated derivatives of 2-thiophenytoin in good yields (4b–4g). We were unable to selectively N3-alkylate 2-thiophenytoin with ethyl acrylate at both room temperature and 70°C under the same conditions (4a). Dimethyl and diethyl fumarates cannot work as Michael acceptors and were hydrolyzed to fumaric acid under reaction conditions.     

Reaction of Dimethyl Acetylenedicarboxylate With 2-Mercaptoperimidine and 2-Mercaptobenzimidazole

A mixture of equimolar quantities of dimethyl acetylenedicarboxylate ( 2 ) with either 2-mercaptoperimidine ( 1 ) or 2-mercaptobenzimidazole ( 5 ) was heated in absolute benzene in the presence of triphenylphosphine as a catalyst under reflux conditions for 1 h (the reaction was monitored by TLC until the consumption of the starting materials). The solvent was concentrated under vacuum and the residue was subjected to chromatographic plates using toluene-ethylacetate (2:1) as an eluent. The products in each reaction were separated as two migrating zones. Each zone was removed from the plate and recrystallized from the appropriate solvent. The products of the first reaction are 10-methoxy-11-oxo-11H-8-thia-7,11a-diaza-benzo[de]anthracene-9-carboxylic acid methyl ester ( 3 ) and 8-thia-7,10a-diaza-cyclopenta[a]phenalene-9,10-dicarboxylic acid dimethyl ester ( 4 ), while the products of the second reaction are 3-methoxy-4-oxo-4H-1-thia-4a,9-diaza-fluorene-2-carboxylic acid methyl ester ( 10 ) and benzo[4, 5]imidazo[2,1-b]thiazole-2,3-dicarboxylic acid dimethyl ester ( 11 ). The mechanisms of the observed reactions are suggested.     

Kondensierte Heterocyclen aus β-Isothiocyanatoketonen und Aminocarbonsäuren

On reaction of glycine, anthranilic acid and anthranilamide respectively with 4-isothiocyanato-4-methyl-2-pentanone (1), derivatives of condensed heterocycles (oxazolopyrimidine5, pyrimidobenzoxazine7 a, pyrimidobenzodiazine7 c) are formed. The same holds for the reaction of dithiocarbamates, prepared from glycine and CS₂ in aqueous NaOH, with 4-methyl-3-penten-2-one and cinnamaldehyde respectively (12 a, b). The reaction of hot dimethylformamide with7 a leads under initial aminolysis to pyrimidine-anthranildimethylamide2 i; this is subsequently transformed partly through methylpyrimidine-pyridine rearrangement into the N-4-pyridine-anthranil-N,N-dimethylamide10 d, partly under further aminolysis byDMF followed by rearrangement to the dimethylaminodihydro-2(1H)-pyridinethione10 c. 5 is converted to dihydro-4-methylamino-2(1H)-pyridinethione (10 a) in boiling hexanol and2 c to n-hexyl-3-(tetrahydrothioxo-pyridylamino)-propionate (10 b).     

Microwave-Assisted Preparation of 2-Substituted Benzothiazoles

Abstract

2-Substituted benzothiazoles ( 3a–h ) were prepared from the condensation reaction of 2-aminothiophenol 1 with aldehydes 2 in the presence of P-Ts-OH and graphite on the surface of solid mineral supports without using any oxidizing agent under microwave irradiation.     

Kondensierte Heterocyclen aus β-Isothiocyanatoketonen und Aminocarbons?uren

On reaction of glycine, anthranilic acid and anthranilamide respectively with 4-isothiocyanato-4-methyl-2-pentanone (1), derivatives of condensed heterocycles (oxazolopyrimidine5, pyrimidobenzoxazine7 a, pyrimidobenzodiazine7 c) are formed. The same holds for the reaction of dithiocarbamates, prepared from glycine and CS₂ in aqueous NaOH, with 4-methyl-3-penten-2-one and cinnamaldehyde respectively (12 a, b). The reaction of hot dimethylformamide with7 a leads under initial aminolysis to pyrimidine-anthranildimethylamide2 i; this is subsequently transformed partly through methylpyrimidine-pyridine rearrangement into the N-4-pyridine-anthranil-N,N-dimethylamide10 d, partly under further aminolysis byDMF followed by rearrangement to the dimethylaminodihydro-2(1H)-pyridinethione10 c. 5 is converted to dihydro-4-methylamino-2(1H)-pyridinethione (10 a) in boiling hexanol and2 c to n-hexyl-3-(tetrahydrothioxo-pyridylamino)-propionate (10 b).     

A Convenient Route to (E)-α,β-Unsaturated Methyl Ketones

Aldehydes are converted into (E)-α,β-unsaturated methyl ketones in good yield and with a high E stereoselectivity using α,α-bis(trimethylsilyl) N-tert-butyl acetimine 3. The reaction was mediated by a catalytic amount of tetrabutylammonium fluoride (TBAF) under mild conditions. The disilylated reagent 3 is easily generated from N-tert-butylacetimine, lithium diisopropylamide (LDA), and chlorotrimethylsilane. The mechanism of the reaction is discussed.     

Reactivite Des α -Phosphonylketones Dans la Reaction de Gewald: Synthese de Nouveaux Derives de L′aminophosphonothiophene

The reaction of α -phosphonylketones 1 with active methylenenitriles 2 leads to phosphonoalkylidenes 3 . The reaction of compounds 3 with sulfur under basic conditions leads to the new 2-amino-4-phosphonothiophenes 4 . The structure of all obtained products was confirmed by NMR (¹H, ³¹P, ¹³C) and IR spectroscopy, and in some cases by mass spectrometry.     

Efficient Synthesis of Ferrocenylquinolines via the Friedländer Reaction

Acylferrocenes 2a–c reacted with ortho-aminoarylaldehydes 1a–e via the Friedländer condensation reaction to afford the corresponding ferrocenylquinolines 3a–o in moderate yields in the presence of sodium ethoxide (30 mmol%) under mild reaction conditions. Under the same reaction conditions, 1,1′-diacetylferrocene 2d and 1,1′-dipropionylferrocene 2e reacted with ortho-aminoaldehydes 1a–e to afford the corresponding 1,1′-bis(substituted quinolin-2-yl)ferrocene derivatives 3p–t. The structures of compounds 3a–t were determined and characterized by infrared, ¹H NMR, mass spectrometry, and elemental analysis. The crystal structures of 3e and 3q were determined by x-ray crystallography.     

Chemo- and Regioselective 1,3-Dipolar Cycloaddition of 2-Diazopropane over 1,4-Benzoquinone: Synthesis of New Pyrazoloquinones

Abstract

1,3-Dipolar cycloaddition reaction of 2-diazopropane 1 with 1,4-benzoquinone 2 carried out at ?20 °C led to a minor mono-cycloadduct 4 and mixture of bis-cycloadducts 6 and 7. The same addition realized with 3H-pyrazole 7 at ?60 °C for 2 h yields a mixture of compounds 8 and 9 and results in O-alkylation. The reaction of 3H-pyrazoles 4 and 7 with dimethylsulfoxide and oxalyl chloride under Swern conditions led to pyrazolenines 11 and 12.     

A green development of Bernthsen 9-substituted acridine synthesis in the absence of solvent catalyzed by p-toluenesulphonic acid (p-TSA)

Abstract

Bernthsen reaction has been carried out under microwave irradiation in the presence of p-TSA (10 mol%) as catalyst in a solventless reaction to provide 9-substituted acridines. In the present report, time economy and better yields as compared to conventional Bernthsen reaction are described.     

Synthesis of Novel Spin Labeled Analogues of N-(Trifluoroacetyl)Daunorubicin

Three novel spin labeled N-(trifluoroacetyl) daunorubicins 6–8 have been synthesized under mild reaction condition in good yields. The antitumor activity of compound 6 and 8 were evaluated in vitro.     

Water-mediated,green, and efficient synthesis of bisquinolones under catalyst-free conditions

Water-mediated, green, and efficient synthesis involving condensation of 4-hydroxy-1-methylquinoline-2(1H)-one (3) with different aromatic and heterocyclic aldehydes (4a–n) leading to 3,3′-(arylmethylene)-bis-(4-hydroxy-1-methylquinolin-2(1H)-one) 5(a–n) under catalyst-free conditions is described. This reaction has an easy workup without using column chromatography and provides excellent yields of the products in shorter reaction times. It does not require any catalyst and uses water as the medium which is the greenest solvent. 3 required in this work was itself obtained by condensation of N-methylaniline (1) with malonic acid (2) in the presence of POCl₃ using a previously reported procedure.     

Syntheses of Novel Hexahomotrithiacalix[3]arenes

The first synthesis of the C ₃ -symmetrical p-tert-butylhexahomotrithiacalix[3]arene 7d via one-pot procedure by the reaction of 2,6-bis(chloromethyl)-p-tert-butylphenol 8d with sodium sulfide nanohydrate under high-dilution conditions is reported. Also, hexahomotrithiacalix[3]arenes 7d-f (where d-f designate the type of the substituents R at the p-positions of the phenolic rings: d, R=t-Bu; e, R=CH₃; f, R=Cl) were synthesized via a convergent approach in good yield by the [2+1] cyclization reaction of 2,6-bis(chloromethyl)phenol monomers 8d-f and bis(chloromethyl)phenol dimers 15d-f in presence of sodium sulfide nanohydrate under high-dilution conditions. The structures of 7d-f were determined by ¹H, ¹³C NMR, MS and elemental analysis. A preliminary study of the binding properties of 7d with alkali- and heavy metal cations using biphasic picrate extraction method showed only weak abilities to bind the cations examined.     

Formation of (±)-1,2-O-Ethylidene-myo-Inositol During the Reaction Between Triethyl Orthoformate and myo-Inositol in DMSO

Besides myo-inositol monoorthoformate (1), (±)-1,2-O-ethylidene-myo-inositol (2) was obtained as another product in the reaction between triethyl orthoformate and myo-inositol in DMSO catalyzed by acid under N₂     

Synthesis of Fused Tetrazolo[1,5‐c] pyrrolo[3,2‐e]pyrimidines and Their Reductive Conversion to New 4‐Aminopyrrolo[2,3‐d]pyrimidines

Some new 7,9‐substituted 7H‐1,2,3,4‐tetrazolo[1,5‐c]pyrrolo[3,2‐e]pyrimidines 5 have been synthesized either by diazotization of 4‐hydrazino‐5,7‐disubstituted‐7H‐pyrrolo[2,3‐d]pyrimidines 4 obtained by hydrazinolysis of 4‐chloro‐5,7‐disubstituted 7H‐pyrrolo[2,3‐d]pyrimidines 3 or via a substitution reaction between 3 and sodium azide. 5,7‐Disubstituted‐7H‐pyrrolo[2,3‐d]pyrimidin‐4(3H)‐ones 2 were obtained by cyclocondensation of 1,4‐disubstituted 2‐amino‐3‐cyanopyrroles 1 with formic acid, which, on chlorination using phosphorus oxychloride, afforded 3. 2‐Amino‐3‐cyanopyrroles 1 were synthesized from the reaction between (2-bromo-1-(4-fluorophenyl) ethylidene) propanedinitrile and substituted aromatic amines under Gewald reaction conditions. A novel route for the synthesis of 4‐amino‐5,7‐disubstituted‐7H‐pyrrolo[2,3‐d]pyrimidines 6 by the reductive ring cleavage of 5 has been reported.     

Detection of Chemical Warfare Nerve Agents via a Beckmann Fragmentation of Aldoxime

Abstract

A new (E)-pyrene-1-carbaldehyde O-tert-butyldimethylsilyl oxime 3 was synthesized for the detection of chemical warfare nerve agents, O-isopropyl methylphosphonofluoridate (GB) and O-pinacolyl methylphosphonofluoridate (GD). ¹H NMR spectrum showed that the tert-butyldimethylsilyl (TBDMS) group was deprotected using TBAF and the oximate supernucleophile was made. Upon addition of chemical warfare agents (GB and GD) (50 mol%), the reaction was completely finished within 5 min and also the color change of reaction mixture was observed under a hand-held UV lamp with the naked eye.