The dipolar route to naphtho[2,1‐c]isoxazoles from the baylis‐hillman adducts of 2‐alkynylbenzaldehydes

A new synthesis of 4‐carbomethoxynaphtho[2,1‐c]isoxazoles 4a‐d from methyl 3‐(alkynylphenyl)‐2‐nitromethyl‐2‐propenoates 2a‐d by the intramolecular nitrile oxide cycloaddition is described. The latter are readily obtained from 2‐alkynylbenzaldehydes through the Baylis‐Hillman adduct acetates 1a‐d followed by nucleophilic substitution of nitrite anion.     

1,8‐Diazafloren‐9‐one with alkyl and aryl isocyanides in the presence of acetylenic esters: A facile synthesis of γ‐spiroiminolactones

The 1:1 intermediate generated by the addition of alkyl and aryl isocyanides to dialkyl acetylenedicarboxylate is trapped by 1,8‐diazafloren‐9‐one to yield iminolactones in good yields.     

Synthesis and characterization of 4‐aryl‐5‐(1‐aryl‐2‐methyl‐2‐nitropropyl)‐1,2,3‐selenadiazoles

The synthesis of a new set of selenadiazoles, 4‐aryl‐5‐(1‐aryl‐2‐methyl‐2‐nitropropyl)‐1,2,3‐selenadiazoles ( 4 ) derived from 2‐[4‐methyl‐4‐nitro‐1,3‐diarylpentylidene]‐1‐hydrazinecarboxamide ( 3 ) has been reported. THF has been found to be the solvent of choice for this reaction. Structural features of 3 and 4 have been analyzed by NMR and X‐ray techniques.     

Synthesis and tautomerization of 6,7‐dihydro‐(1,2,3)‐triazolo[1,5‐a]pyrimidines

The condensation of 5‐amino‐4‐phenyl‐1,2,3‐triazole ( 1 ) with chalcones 2a‐e or 3‐dimethylamino‐propiophenone ( 4f ) leads to the 6,7‐dihydro‐(1,2,3)‐triazolo[1,5‐a]pyrimidines 3a‐f. The equilibrium of 3 and the tautomeric 4,7‐dihydro‐(1,2,3)‐triazolo[1,5‐a]pyrimidines 3′ is described.     

Synthesis of a library of 1,2,3,7‐tetrasubstituted indolizines using poly(ethylene glycol) as soluble support

A library of 1,2,3,7‐tetrasubstituted indolizines has been synthesized using poly(ethylene glycol) (PEG) as soluble polymer support. The PEG‐bound pyridinium salts reacted with alkenes or alkynes in the presence of Et₃N via 1,3‐dipolar cycloaddition to give PEG‐bound indolizine derivatives, which were cleaved by 1 % KCN/MeOH to afford 1,2,3,7‐tetrasubstituted indolizines in good to excellent yields.     

Ready access to 7,8‐dihydro‐ and 1,2,3,4‐tetrahydro‐1,6‐naphthyridine‐5(6H)‐ones from simple pyridine precursors

Short pathways are described for the synthesis of a representative example of each of the 7,8‐dihydro‐and 1,2,3,4‐tetrahydro‐1,6‐naphthyridine‐5(6H)‐one ring systems from simple pyridine precursors. An attempted synthesis of the related 4,6‐dihydro‐1,6‐naphthyridin‐5(1H)‐one ring system from a common intermediate was unsuccessful.     

Some nucleophilic substitutions in 2‐cyano‐3‐nitroimidazo[1,2‐a]pyridine

In some nucleophilic substitution reactions of 2‐cyano‐3‐nitroimidazo[1,2‐a]pyridine, nitrogen (alkylamines, guanidine) and oxygen nucleophiles (alkoxides) underwent substitution of the 2‐cyano group, while sulfur nucleophiles (alkylthiols) underwent substitution of the 3‐nitro group.     

Synthesis of 1‐(substituted phenylcarbonyl/sulfonylamino)‐1,2,3,6‐tetrahydropyridine‐5‐carboxylic acid diethylamides as potential anti‐inflammatory agents

Fifteen novel 1‐(substituted phenylcarbonyl/sulfonylamino)‐1,2,3,6‐tetrahydro‐ pyridine‐5‐carboxylic acid diethylamide ( 7, 15 ) were synthesized in fair to good yields via sodium borohydride reduction of the corresponding 1‐(substituted phenylcarbonyl/ sulfonylimino)‐3‐diethylcarbamoyl pyridinium ylides ( 6, 14 ) in absolute ethanol.     

Convenient synthesis of some 2‐substituted 4(3H)‐quinazolinone derivatives

A series of 2‐substituted‐4(3H)‐quinazolinones 13‐20 has been synthesized in good yields using the reaction of double lithiated 2‐methylquinazolinone‐4 with a variety of aromatic aldehydes. They have been easily transformed in high yields into the corresponding 2‐substituted conjugated derivatives 21‐28 bearing terminal aryl groups by F₃CCOOH mediated dehydration.     

Catalyst and pressure dependent reductive cyclizations for the diastereo‐selective synthesis of hexahydropyrrolo[1,2‐a]quinoline‐5‐carboxylic esters

A diastereoselective synthesis of 1,2,3,3a,4,5‐hexahydropyrrolo[1,2‐a]quinoline‐5‐carboxylic esters has been developed using a tandem reduction‐double reductive amination reaction. The nitro dicarbonyl cyclization substrates were synthesized by alkylation of methyl (2‐nitrophenyl)acetate with 2‐bromomethyl‐1,5‐hexadiene derivatives, followed by ozonolysis. Catalytic hydrogenation of each substrate gave the target heterocycle, along with a deacylated product and an adduct resulting from capture of the intermediate hydroxylamine by the side chain carbonyls. The product ratio varied dramatically with the catalyst and the hydrogen pressure. Cyclization to the title compounds was highly diastereoselective, producing each hexahydropyrrolo[1,2‐a]‐quinoline as a single stereoisomer with the all‐cis geometry. The competing processes have not been observed in previous heterocyclization studies but can be attributed to greater strain in the system, which slows the final ring closure.     

Synthesis of propionamide pyridine and pyridine n‐oxide ligands

A new set of pyridine and pyridine N‐oxides functionalized with N,N‐dimethylpropionamide pendant groups in the 2‐ and 2,6‐positions have been prepared from the combination of 2‐chloromethylpyridine and 2,6‐bis(chloromethyl) pyridine with α‐lithio N,N‐dimethyl acetamide. The coordination interaction between 2‐(N,N‐dimethylpropionamide) pyridine N‐oxide ( 10 ) and Tb(NO₃)₃ has been unambiguously defined via single crystal X‐ray diffraction analysis of Tb( 10 )(NO₃)₃(H₂O).     

A mechanistic approach to photochemical behavior of 4‐anisyl‐4‐methyl‐2,6‐diphenyl‐4H‐thiopyran‐1,1‐dioxide

Photoisomerization of 4‐anisyl‐4‐methyl‐2,6‐diphenyl‐4H‐thiopyran‐1,1‐dioxide is described in the presence of a sensitizer and new mechanistic features are proposed. The relative molar ratios of the stereoselective photoproducts compared in the presence and the absence of sensitizer in different concentrations of the starting material using hplc. The results observed are discussed on the basis of a triplet excited state thiadi‐π‐methane rearrangement.     

Biginelli‐like three component reaction: Synthesis of some new ethyl 6‐ethoxycarbonylmethyl‐4‐aryl‐2‐oxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxylate derivatives

In the context of our high‐throughput organic synthesis program, we have studied the reactivity of special β‐keto esters toward the Biginelli reaction. We have found that a diethyl‐3‐oxoglutarate reacts with one molecule of urea and one molecule of aldehyde under solvent‐free conditions to give a new family of 3,4‐dihydropyrimidin‐2(1H)‐ones in good yields.     

New access to thiazolo[4,5‐d]pyrimidine derivativess

4‐Amino‐5‐bromo‐2‐substituted‐aminopyrimidines are readily obtained from the newly prepared 5‐bromo‐2,4‐dichloro‐6‐methylpyrimidine by sequential treatment with ethanolic ammonia and secondary amines. These compounds were successfully reacted with various isothiocyanates in the presence of sodamide in DMF to form the new thiazolo[4,5‐d] pyrimidine derivatives.     

Reaction of 4‐substituted thiosemicarbazides with (2,4,7‐trinitro‐9H‐fluoren‐9‐ylidene)propanedinitrile

4‐Substituted thiosemicarbazides 4a‐c reacted with (2,4,7‐trinitro‐9H‐fluoren‐9‐ylidene)‐propanedinitrile ( 2 ) in pyridine with admission of air to form spiro[fluorene‐9,3′‐(1,2,4‐triazole)]derivatives 5a‐c and (4‐substituted thiosemicarbazono)propanedinitriles 6a‐c in modest yields. 2,4,7‐Trinitro‐9‐fluorenone ( 8 ) as well as one reduction product thereof and of 2 , namely compounds 9 and 10 , respectively are also found. A rationale for the conversions observed is presented.     

New synthesis,x‐ray structural determination,conformational analysis and anomeric effect study of 3,7‐di (3‐nitrophenyl)‐1,5‐dioxa‐3,7‐diazacyclooctane

3,7‐Di(3‐nitrophenyl)‐1,5‐dioxa‐3,7‐diazacyclooctane was prepared from 3‐nitroaniline and formaldehyde in acetonitrile. Conformational behavior of ring inversion of the molecule was studied so it prefers a crown conformation. The evaluated ΔG^* was approximately 58.0 ± 1.0 kJ/mole. The X‐ray structure determination of the compound shows a crown conformation, in line with two‐anomeric effect in N‐C‐O moiety.     

Azulene‐substituted pyranylium salts. Syntheses and products characterization

The synthesis of 4‐azulene‐substituted 2,6‐diphenyl‐ and 2,6‐dimethyl‐pyranylium salts and 2‐azulenesubstituted 4,6‐dimethyl‐pyranylium salts by nucleophilic substitution at pyranylium moiety with various azulenes was studied. The starting materials for 2,6‐diphenyl derivatives were 4 chlorinated pyranylium salts. They were obtained by the halogenation with PCl₅ of corresponding pyranones and were used either in situ or after separation. For the synthesis of dimethyl derivatives the corresponding pyranones were treated with POCl₃ and the resulted intermediate was reacted in situ with azulene. In the aim to study the influence of dihedral angle between azulene and pyranylium planes on the recorded spectra, both moieties were adequately substituted. The obtained results were in accord with the calculated values.     

An efficient one‐pot synthesis of 5‐aryl substituted 2‐amino‐5,8‐dihydropyrido[2,3‐D] pyrimidin‐4,7‐diones under microwave irradiationl without catalyst

A series of 5‐aryl substituted 2‐amino‐5,8‐dihydropyrido[2,3‐d]pyrimidin‐4,7‐diones were synthesized through one‐pot condensation of 2,6‐diaminopyrimidin‐4‐one, aldehyde and Meldrum's acid using glycol as energy transfer agent under microwave irradiation without catalyst. The one‐pot protocol in the absence of catalyst has the advantage of good yield (86‐95%), short route and reaction time (3‐6 min) and environmentally friendly.     

One‐pot synthesis of 2‐acylimino‐3‐aryl‐1,3‐thiazoline derivatives in aqueous media

The one‐pot two‐step synthesis for acyliminothiazolines by treatment of N,N'‐substituted thioureas with α‐bromocarbonyl compounds under aqueous media was described. Compared to classical reaction in organic solvents, this method consistently has the advantages of short reaction time and being environmentally friendly.     

Lithiation of N‐protected‐dihydro‐1,4‐benzoxaziness

Lithiation of N‐protected‐2,3‐dihydro‐1,4‐benzoxazines is described. Lithiation of N‐(tert‐butoxycarbonyl)‐2,3‐dihydro‐1,4‐benzoxazine ( 1 ) with BuLi/TMEDA occurred in the α‐position to nitrogen on the heterocyclic ring, leading to the unexpected ring‐opened product 3 . On the other hand, lithiation of N‐methyl‐2,3‐dihydro‐1,4‐benzoxazine ( 4 ) took place at the oxygen‐adjacent ortho‐position of the aromatic ring.