3‐Benzyl‐2‐(4‐fluorophenyl)‐1,3‐thiazolidin‐4‐one

The title compound, C₁₆H₁₄FNOS, crystallizes with Z′ = 2 in the space group P2₁/c. In one of the two independent molecules, the heterocyclic ring is effectively planar, but in the other molecule this ring adopts an envelope conformation. The molecules are weakly linked by two C—H...O hydrogen bonds to form C₂²(14) chains. Comparisons are made with some symmetrically substituted 2‐aryl‐3‐benzyl‐1,3‐thiazolidin‐4‐ones.     

Chemoselectivity of the Reactions of Diazomethanes with 5‐Benzylidene‐3‐phenylrhodanine

The reactions of 5‐benzylidene‐3‐phenylrhodanine ( 2 ; rhodanine=2‐thioxo‐1,3‐thiazolidin‐4‐one) with diazomethane ( 7a ) and phenyldiazomethane ( 7b ) occurred chemoselectively at the exocyclic C?C bond to give the spirocyclopropane derivatives 9 and, in the case of 7a , also the C‐methylated products 8 (Scheme 1). In contrast, diphenyldiazomethane ( 7c ) reacted exclusively with the C?S group leading to the 2‐(diphenylmethylidene)‐1,3‐thiazolidine 11 via [2+3] cycloaddition and a ‘two‐fold extrusion reaction’. Treatment of 8 or 9b with an excess of 7a in refluxing CH₂Cl₂ and in THF at room temperature in the presence of [Rh₂(OAc)₄], respectively, led to the 1,3‐thiazolidine‐2,4‐diones 15 and 20 , respectively, i.e., the products of the hydrolysis of the intermediate thiocarbonyl ylide. On the other hand, the reactions with 7b and 7c in boiling toluene yielded the corresponding 2‐methylidene derivatives 16, 21a , and 21b . Finally, the reaction of 11 with 7a occurred exclusively at the electron‐poor C?C bond, which is conjugated with the C?O group. In addition to the spirocyclopropane 23 , the C‐methylated 22 was formed as a minor product. The structures of the products (Z)‐ 8, 9a, 9b, 11 , and 23 were established by X‐ray crystallography.     

Hydriodic Acid‐Mediated Cyclization of α‐Substituted Secondary 2‐Ethenylbenzamides: Synthesis of 2‐Substituted 2,3‐Dihydro‐3,3‐dimethyl‐1H‐isoindol‐1‐ones and 3,3‐Disubstituted (E)‐1‐(Arylimino)‐1,3‐dihydroisobenzofurans

A new and facile method for the preparation of 2‐substituted 2,3‐dihydro‐3,3‐dimethyl‐1H‐isoindol‐1‐ones 3 and 3,3‐disubstituted (E)‐1‐(arylimino)‐1,3‐dihydroisobenzofurans 6 has been developed. Thus, treatment of N‐alkyl(or aryl)‐2‐(1‐methylethen‐1‐yl)benzamides 2 with concentrated hydriodic acid (HI) in MeCN at room temperature afforded 3 . Similar treatment of N‐aryl‐2‐(1‐phenylethen‐1‐yl)benzamide 5 with concentrated HI at 0° afforded 6 .     

Chemoselectivity in the Reaction of 2‐Diazo‐3‐oxo‐3‐phenylpropanal with Aldehydes and Ketones

The chemoselectivity in the reaction of 2‐diazo‐3‐oxo‐3‐phenylpropanal ( 1 ) with aldehydes and ketones in the presence of Et₃N was investigated. The results indicate that 1 reacts with aromatic aldehydes with weak electron‐donating substituents and cyclic ketones under formation of 6‐phenyl‐4H‐1,3‐dioxin‐4‐one derivatives. However, it reacts with aromatic aldehydes with electron‐withdrawing substituents to yield 1,3‐diaryl‐3‐hydroxypropan‐1‐ones, accompanied by chalcone derivatives in some cases. It did not react with linear ketones, aliphatic aldehydes, and aromatic aldehydes with strong electron‐donating substituents. A mechanism for the formation of 1,3‐diaryl‐3‐hydroxypropan‐1‐ones and chalcone derivatives is proposed. We also tried to react 1 with other unsaturated compounds, including various olefins and nitriles, and cumulated unsaturated compounds, such as N,N′‐dialkylcarbodiimines, phenyl isocyanate, isothiocyanate, and CS₂. Only with N,N′‐dialkylcarbodiimines, the expected cycloaddition took place.     

Regiospecific synthesis,structure and electron ionization mass spectra of 1,3‐thiazolidin‐4‐ones containing the acridine skeleton

The synthesis of regioisomeric 3‐alkyl(aryl)‐2‐(acridin‐9′‐yl)imino‐1,3‐thiazolidin‐4‐ones ( 8b‐i ) and 2‐alkyl(aryl)imino‐3‐(acridin‐9′‐yl)‐1,3‐thiazolidin‐4‐ones ( 11a‐i ) was performed by the reaction of 3‐(acridin‐9‐yl)‐1‐alkyl(aryl)thioureas 5a‐i with methyl bromoacetate and bromoacetyl bromide, respectively, via the corresponding isothiourea hydrobromides with excellent regioselectivity. The structure, NMR spectra and mass spectrometric behavior of the resulting compounds are discussed.     

Studies on 4‐Thiazolidinones: Scope of the Reactions of 3‐Aryl‐2‐thioxo‐1,3‐thiazolidin‐4‐ones with Cyanide and Cyanate Ions

Treatment of 3‐aryl‐2‐thioxo‐1,3‐thiazolidin‐4‐ones 1 with CN^? and NCO^? effected the ring cleavage providing [(cyanocarbonothioyl)amino]benzenes 4 and arylisothiocyanates 5 , respectively. Similar treatment of 5‐(2‐aryl‐2‐oxoethyl) derivatives 2 afforded 2,4‐bis(2‐aryl‐2‐oxoethylidene)cyclobutane‐1,3‐diones 6 along with each of the preceding products. Treatment of the respective (E,Z)‐5‐(2‐aryl‐2‐oxoethylidene) analogues 3b and 3c with CN^? gave 4b and 4c and 2‐(arylcarbonyl)‐2‐methoxy‐4‐oxopentanedinitriles 7b and 7c , in addition to 3,6‐bis[2‐(4‐chlorophenyl)‐1‐methoxy‐2‐oxoethylidene]‐1,4‐dithiane‐2,5‐dione 8c , which has been generated from 3c . Reactions of 3c or 3d with NCO^? provided 5c or 5d , together with 8c or 8d as pure isomers. In the formation of the MeO products 7 and 8 , the solvent (MeOH) has participated. Structures of these products are based on microanalytical and spectroscopic data. Rationalizations for the above transformations are given.     

(Z)‐5‐[(5‐Methyl‐1H‐imidazol‐4‐yl)methylidene]‐2‐sulfanylidene‐1,3‐thiazolidin‐4‐one monohydrate: a three‐dimensional hydrogen‐bonded framework structure

The non‐H atoms in the organic component of the title compound, C₈H₇N₃OS₂·H₂O, are almost coplanar, as the dihedral angle between the two ring planes is only 1.8 (2)°; there is a wide C—C—C angle of 127.8 (3)° at the methine C atom linking the two rings. The molecular components are linked into a three‐dimensional framework structure by two‐centre hydrogen bonds of N—H...O and O—H...N types, together with a three‐centre O—H...(N,S) system. Comparisons are made with some (Z)‐5‐arylmethylidene‐2‐sulfanylidene‐1,3‐thiazolidin‐4‐ones.     

Original recyclization of S‐phenacyl derivatives of 4‐acylamino‐2‐mercapto‐1,3‐oxazoles and their analogues

Readily accessible acylamino(chloro)acetophenones, if treated with sodium rhodanide and α‐halogenocarbonyl compounds, provide 4‐acylamino‐5‐aryl‐2‐mercapto‐1,3‐oxazole derivatives which undergo recyclization on heating in polyphosphoric acid to give substituted 1,3‐thiazol‐2(3H)‐ones or 1,3‐thiazolidin‐2,4‐diones containing 2‐alkyl(aryl)‐5‐aryl‐1,3‐oxazol‐4‐yl residues at the N³ atom. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:432–437, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20317     

New Approaches to the Synthesis of 4‐(2‐Aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones and 3‐Ureidoindoles and a Study of Their Interconversion

3‐Alkyl/aryl‐3‐ureido‐1H,3H‐quinoline‐2,4‐diones ( 2 ) and 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) react in boiling concentrated HCl to give 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ). The same compounds were prepared by the same procedure from 2‐alkyl/aryl‐3‐ureido‐1H‐indoles ( 4 ), which were obtained from the reaction of 3‐alkyl/aryl‐3‐aminoquinoline‐2,4(1H,3H)‐diones ( 1 ) with 1,3‐diphenylurea or by the transformation of 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) and 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ) in boiling AcOH. The latter were converted into 1,3‐bis[2‐(2‐oxo‐2,3‐dihydro‐1H‐imidazol‐4‐yl)phenyl]ureas ( 5 ) by treatment with triphosgene. All compounds were characterized by ¹H‐ and ¹³C‐NMR and IR spectroscopy, as well as atmospheric pressure chemical‐ionisation mass spectra.     

Synthesis of 3‐(ω‐Hydroxyalkoxy)isobenzofuran‐1(3H)‐ones by Trifluoroacetic Acid‐Mediated Lactonization of tert‐Butyl 2‐(1,3‐Dioxol‐2‐yl)‐ or 2‐(1,3‐Dioxan‐2‐yl)benzoates

An efficient two‐step method for the preparation of 3‐(2‐hydroxyethoxy)‐ or 3‐(3‐hydroxypropoxy)isobenzofuran‐1(3H)‐ones 3 has been developed. Thus, the reaction of 1‐(1,3‐dioxol‐2‐yl)‐ or 1‐(1,3‐dioxan‐2‐yl)‐2‐lithiobenzenes, generated in situ by the treatment of 1‐bromo‐2‐(1,3‐dioxol‐2‐yl)‐ or 1‐bromo‐2‐(1,3‐dioxan‐2‐yl)benzenes 1 with BuLi in THF at ?78°, with (Boc)₂O afforded tert‐butyl 2‐(1,3‐dioxol‐2‐yl)‐ or 2‐(1,3‐dioxan‐2‐yl)benzoates 2 , which can subsequently undergo facile lactonization on treatment with CF₃COOH (TFA) in CH₂Cl₂ at 0° to give the desired products in reasonable yields.     

Novel and Stereospecific Synthesis of (2S)‐3‐(2,4,5‐Trifluorophenyl)propane‐1,2‐diol from D‐Mannitol

A stereospecific synthesis of (2S)‐3‐(2,4,5‐trifluorophenyl)propane‐1,2‐diol from D ‐mannitol has been developed. The reaction of 2,3‐O‐isopropylidene‐D ‐glyceraldehyde with 2,4,5‐trifluorophenylmagnesium bromide gave [(4R)‐2,2‐dimethyl‐1,3‐dioxolan‐4‐yl](2,4,5‐trifluorophenyl)methanol in 65% yield as a mixture of diastereoisomers (1 : 1). The Ph₃P catalyzed reaction of the latter with C₂Cl₆ followed by reduction with Pd/C‐catalyzed hydrogenation gave (2S)‐3‐(2,4,5‐trifluorophenyl)propane‐1,2‐diol with >99% ee and 65% yield.     

Fe3O4@L‐arginine magnetic nanoparticles: A novel and magnetically retrievable catalyst for the synthesis of 1′3‐diaryl‐2N‐azaphenalene

The catalytic activity of l ‐arginine‐coated nano‐Fe₃O₄ particles (Fe₃O₄@l ‐arginine) proves they are a novel magnetic catalyst without the use of heat and reflux for the synthesis of 1,3‐diaryl‐2‐N‐azaphenalene derivatives and n‐acyl‐1,3‐diaryl‐2‐N‐azaphenylene derivatives in a one‐pot pseudo‐five‐component condensation reaction of compounds of 2,7‐naphthalene diol, aldehydes, and ammonia derivatives (ammonium acetate or ammonium hydrogen phosphate) and solvent (water and alcohol) with high yield and short reaction times, economical, and simple workup. The structure and magnetic properties of the obtained nanoparticles were characterized via Fourier transform infrared spectroscopy (IR) and field emission scanning electron microscopy (FE‐SEM). The results demonstrated that the average size of the synthesized magnetite nanoparticles is about 21 nm. In addition, the heterogeneous catalyst can be easily recovered magnetically and can be reused for further runs without significant loss of its catalytic activity.     

Synthesis of Bis‐Heterocyclic 1H‐Imidazole 3‐Oxides from 3‐Oxido‐1H‐imidazole‐4‐carbohydrazides

The reaction of 1H‐imidazole‐4‐carbohydrazides 1 , which are conveniently accessible by treatment of the corresponding esters with NH₂NH₂?H₂O, with isothiocyanates in refluxing EtOH led to thiosemicarbazides (=hydrazinecarbothioamides) 4 in high yields (Scheme 2). Whereas 4 in boiling aqueous NaOH yielded 2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thiones 5 , the reaction in concentrated H₂SO₄ at room temperature gave 1,3,4‐thiadiazol‐2‐amines 6 . Similarly, the reaction of 1 with butyl isocyanate led to semicarbazides 7 , which, under basic conditions, undergo cyclization to give 2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐ones 8 (Scheme 3). Treatment of 1 with Ac₂O yielded the diacylhydrazine derivatives 9 exclusively, and the alternative isomerization of 1 to imidazol‐2‐ones was not observed (Scheme 4). It is important to note that, in all these transformations, the imidazole N‐oxide residue is retained. Furthermore, it was shown that imidazole N‐oxides bearing a 1,2,4‐triazole‐3‐thione or 1,3,4‐thiadiazol‐2‐amine moiety undergo the S‐transfer reaction to give bis‐heterocyclic 1H‐imidazole‐2‐thiones 11 by treatment with 2,2,4,4‐tetramethylcyclobutane‐1,3‐dithione (Scheme 5).     

Heterocyclic tautomerism: reassignment of two crystal structures of 2‐amino‐1,3‐thiazolidin‐4‐one derivatives

The structures of 5‐(2‐hydroxyethyl)‐2‐[(pyridin‐2‐yl)amino]‐1,3‐thiazolidin‐4‐one, C₁₀H₁₁N₃O₂S, (I), and ethyl 4‐[(4‐oxo‐1,3‐thiazolidin‐2‐yl)amino]benzoate, C₁₂H₁₂N₂O₃S, (II), which are identical to the entries with refcodes GACXOZ [Váňa et al. (2009). J. Heterocycl. Chem. 46 , 635–639] and HEGLUC [Behbehani & Ibrahim (2012). Molecules, 17 , 6362–6385], respectively, in the Cambridge Structural Database [Allen (2002). Acta Cryst. B 58 , 380–388], have been redetermined at 130 K. This structural study shows that both investigated compounds exist in their crystal structures as the tautomer with the carbonyl–imine group in the five‐membered heterocyclic ring and an exocyclic amine N atom, rather than the previously reported tautomer with a secondary amide group and an exocyclic imine N atom. The physicochemical and spectroscopic data of the two investigated compounds are the same as those of GACXOZ and HEGLUC, respectively. In the thiazolidin‐4‐one system of (I), the S and chiral C atoms, along with the hydroxyethyl group, are disordered. The thiazolidin‐4‐one fragment takes up two alternative locations in the crystal structure, which allows the molecule to adopt R and S configurations. The occupancy factors of the disordered atoms are 0.883 (2) (for the R configuration) and 0.117 (2) (for the S configuration). In (I), the main factor that determines the crystal packing is a system of hydrogen bonds, involving both strong N—H...N and O—H...O and weak C—H...O hydrogen bonds, linking the molecules into a three‐dimensional hydrogen‐bond network. On the other hand, in (II), the molecules are linked via N—H...O hydrogen bonds into chains.     

Synthesis of 2‐Aryl‐5‐oxo‐4‐[2‐(phenylmethylidene)hydrazino]‐2,5‐dihydro‐1H‐pyrrole‐3‐carboxylates by the Reaction between Hydrazones,Acetylenedicarboxylates, and 1‐Aryl‐N,N′‐bis(arylmethylidene)methanediamines

An efficient approach for the preparation of functionalized 2‐aryl‐2,5‐dihydro‐5‐oxo‐4‐[2‐(phenylmethylidene)hydrazino]‐1H‐pyrroles is described. The four‐component reaction between aldehydes, NH₂NH₂?H₂O, dialkyl acetylenedicarboxylates, and 1‐aryl‐N,N′‐bis(arylmethylidene)methanediamines proceeds in EtOH under reflux in good‐to‐excellent yields (Scheme 1). The structures of 4 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS, and, in the case of 4f , by X‐ray crystallography). A plausible mechanism for this type of reaction is proposed (Scheme 2).     

A Convenient Synthesis of 2,3‐Dihydro‐4H‐thiopyrano[2,3‐b]‐, ‐[2,3‐c]‐, or ‐[3,2‐c]pyridin‐4‐ones by the Reaction of the Corresponding 1‐(Chloropyridinyl)alk‐2‐en‐1‐ones with NaSH

2,3‐Dihydro‐4H‐thiopyrano[2,3‐b]pyridin‐4‐ones 4 were prepared by a three‐step sequence from commercially available 2‐chloropyridine ( 1 ). Thus, successive treatment of 1 with ⁱPr₂NLi (LDA) and α,β‐unsaturated aldehydes gave 1‐(2‐chloropyridin‐3‐yl)alk‐2‐en‐1‐ols 2 , which were oxidized with MnO₂ to 1‐(2‐chloropyridin‐3‐yl)alk‐2‐en‐1‐ones 3 . The reactions of 3 with NaSH?n H₂O proceeded smoothly at 0° in DMF to provide the desired thiopyranopyridinones. Similarly, 2,3‐dihydro‐4H‐thiopyrano[2,3‐c]pyridin‐4‐ones 8 and 2,3‐dihydro‐4H‐thiopyrano[3,2‐c]pyridin‐4‐ones 12 were obtained starting from 3‐chloropyridine ( 5 ) and 4‐chloropyridine ( 9 ), respectively.     

Cyclization vs. Elimination Reactions of 5‐Aryl‐5‐hydroxy 1,3‐Diones: One‐Pot Synthesis of 2‐Aryl‐2,3‐dihydro‐4H‐pyran‐4‐ones

2‐Aryl‐2,3‐dihydro‐4H‐pyran‐4‐ones were prepared in one step by cyclocondensation of 1,3‐diketone dianions with aldehydes. The use of HCl (10%) for the aqueous workup proved to be very important to avoid elimination reactions of the 5‐aryl‐5‐hydroxy 1,3‐diones formed as intermediates. The TiCl₄‐mediated cyclization of a 2‐aryl‐2,3‐dihydro‐4H‐pyran‐4‐one with 1,3‐silyloxybuta‐1,3‐diene resulted in cleavage of the pyranone moiety and formation of a highly functionalized benzene derivative.     

Reactions of Imidoyl Isoselenocyanates with Aromatic 2‐Amino N‐Heterocycles and 1‐Methyl‐1H‐imidazole

The reaction of N‐phenylimidoyl isoselenocyanates 1 with 2‐amino‐1,3‐thiazoles 10 in acetone proceeded smoothly at room temperature to give 4H‐1,3‐thiazolo[3,2‐a] [1,3,5]triazine‐4‐selones 13 in fair yields (Scheme 2). Under the same conditions, 1 and 2‐amino‐3‐methylpyridine ( 11 ) underwent an addition reaction, followed by a spontaneous oxidation, to yield the 3H‐4λ⁴‐[1,2,4]selenadiazolo[1′,5′:1,5] [1,2,4]selenadiazolo[2,3‐a]pyridine 14 (Scheme 3). The structure of 14 was established by X‐ray crystallography (Fig. 1). Finally, the reaction of 1‐methyl‐1H‐imidazole ( 12 ) and 1 led to 3‐methyl‐1‐(N‐phenylbenzimidoyl)‐1H‐imidazolium selenocyanates 15 (Scheme 4). In all three cases, an initially formed selenourea derivative is proposed as an intermediate.     

Influence of Cu(II) Ions on the Mechanism of the Ring Transformation of S‐(2‐Oxotetrahydrofuran‐3‐yl)‐N‐(4‐methoxyphenyl)isothiouronium Bromide

The effect of additional Cu(II) ions on the rate of transformation of S‐(2‐oxotetrahydrofuran‐3‐yl)‐N‐(4‐methoxyphenyl)isothiouronium bromide ( 1 ) into 5‐(2‐hydroxyethyl)‐2‐[(4‐methoxyphenyl)imino]‐1,3‐thiazolidin‐4‐one ( 2 ) has been studied in aqueous buffer solutions. The reaction acceleration in acetate buffers is caused by the formation of a relatively weakly bonded complex (K_c = 600 L·mol^?1) of substrate with copper(II) acetate in which the Cu(II) ion acts as a Lewis acid coordinating the carbonyl oxygen and facilitating the intramolecular attack, leading to the formation of intermediate T^±. The formation of the complex of copper(II) acetate with free isothiourea in the fast preequilibrium (K_c) is followed by the rate‐limiting transformation (k_Cu) of this complex. At the high concentrations of the acetate anions, the reaction is retarded by the competitive reaction of these ions with copper(II) acetate to give an unreactive complex [Cu(OAc)₄]^2?_. The influence of Cu(II) ions on the stability of reaction intermediates and the leaving group ability of the alkoxide‐leaving group compared to the Cu(II)‐uncatalyzed reaction is also discussed.     

Synthesis and ring transformation of substituted S‐(1‐phenylpyrrolidine‐2‐ones‐3‐yl)isothiuronium salts to substituted 2‐imino‐5‐[2‐(phenylamino)ethyl]thiazolidin‐4‐ones

Dedicated to Professor Jaromír Kaválek on the occasion of his 65^th birthday Substituted S‐(1‐phenylpyrrolidin‐2‐on‐3‐yl)isothiuronium salts in weakly basic media undergo intramolecular recyclisation reaction in which the γ‐lactam cycle is split and a thiazolidine cycle is formed. A series of six substituted 2‐imino‐5‐[2‐(phenylamino)ethyl]‐thiazolidin‐4‐ones have been prepared by this reaction.