A structural study of 4‐aminoantipyrine and six of its Schiff base derivatives

Six derivatives of 4‐amino‐1,5‐dimethyl‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐3‐one (4‐aminoantipyrine), C₁₁H₁₃N₃O, (I), have been synthesized and structurally characterized to investigate the changes in the observed hydrogen‐bonding motifs compared to the original 4‐aminoantipyrine. The derivatives were synthesized from the reactions of 4‐aminoantipyrine with various aldehyde‐, ketone‐ and ester‐containing molecules, producing (Z)‐methyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]but‐2‐enoate, C₁₆H₁₉N₃O₃, (II), (Z)‐ethyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]but‐2‐enoate, C₁₇H₂₁N₃O₃, (III), ethyl 2‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]cyclohex‐1‐enecarboxylate, C₂₀H₂₅N₃O₃, (IV), (Z)‐ethyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]‐3‐phenylacrylate, C₂₂H₂₃N₃O₃, (V), 2‐cyano‐N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)acetamide, C₁₄H₁₄N₄O₂, (VI), and (E)‐methyl 4‐{[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]methyl}benzoate, C₂₀H₁₉N₃O₃, (VII). The asymmetric units of all these compounds have one molecule on a general position. The hydrogen bonding in (I) forms chains of molecules via intermolecular N—H...O hydrogen bonds around a crystallographic sixfold screw axis. In contrast, the formation of enamines for all derived compounds except (VII) favours the formation of a six‐membered intramolecular N—H...O hydrogen‐bonded ring in (II)–(V) and an intermolecular N—H...O hydrogen bond in (VI), whereas there is an intramolecular C—H...O hydrogen bond in the structure of imine (VII). All the reported compounds, except for (II), feature π–π interactions, while C—H...π interactions are observed in (II), C—H...O interactions are observed in (I), (III), (V) and (VI), and a C—O...π interaction is observed in (II).     

A convenient route to pyridones,pyrazolo[2,3‐a]pyrimidines and pyrazolo[5,1‐c]triazines incorporating antipyrine moiety

Condensation of 4‐aminoantipyrine with ethyl acetoacetate, ethyl benzoylacetate, and ethyl cyanoacetate furnished the corresponding ethyl 3‐(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)aminoacrylate and 2‐cyano‐N‐[(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)]acetamide derivatives. The aminoacrylates derivatives react with acetonitrile and sodium hydride to give 2‐amino‐6‐methyl‐1‐(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)‐4‐pyridone. Reaction of the cyanoacetamide derivative with dimethylformamide‐dimethylacetal (DMF‐DMA) afforded 2‐cyano‐N‐[1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐pyrazol‐4‐yl]‐2‐(N,N‐dimethylamino)methylene acetamide in high yield. Treatment of the latter with 5‐aminopyrazole derivatives afforded the corresponding pyrazolo[2,3‐a]pyrimidines. 2‐cyano‐N‐[(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)]acetamide also reacts with heterocyclic diazonium salts to give the corresponding pyrazolo[5,1‐c]‐1,2,4‐triazine derivatives. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:508–514, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20046     

Asymmetric Reaction of Simple Nitro Compounds with Chiral 1,3‐Oxazolidin‐2‐ones

The chiral oxazolidinone 1 (=[(3aS,6R,7aR)‐tetrahydro‐8,8‐dimethyl‐2‐oxo‐4H‐3a,6‐methano‐1,3‐benzoxazol‐3‐yl](oxo)acetaldehyde) was found to react stereoselectively with simple nitro compounds in the presence of Al₂O₃ or Bu₄NF?3 H₂O (TBAF) as catalysts, affording the diastereoisomeric nitro alcohols 3 – 6 with good asymmetric induction. When Al₂O₃ was used, the (S)‐configuration at the center bearing the OH group was generated, with the relative syn‐configuration for the major diastereoisomers. In the case of the nitro‐aldol reaction catalyzed by TBAF, an opposite asymmetric induction was found for two nitro compounds. In contrast to 1 , compound 12 (=((4R,5S)‐4‐methyl‐2‐oxo‐5‐phenyl‐1,3‐oxazolidin‐3‐yl)(oxo)acetaldehyde), a derivative of Evans auxiliary, gave rise to poor asymmetric induction in Henry reactions.     

Furan ring opening — isocoumarine ring closure: A recyclization reaction of 2‐carboxyaryldifurylmethanes

A general method for the synthesis of isocoumarine derivatives has been developed. Bis(5‐R‐2‐furyl)methylbenzoic acids (R = methyl, ethyl) underwent recyclization and subsequent cyclization into tetracyclic isochromene‐1‐one derivatives under treatment with hydrogen chloride in methanol. It has been shown that intermediate 4‐(5‐R‐furan‐2‐yl)‐3‐(3‐oxo‐3‐R‐propyl)‐isochromene‐1‐ones can be obtained selectively by varying a concentration of the hydrogen chloride and reaction times. In the case of R = tert‐butyl only corresponding 4‐[5‐(tert‐butyl)‐2‐furyl]‐3‐(4,4‐dimethyl‐3‐oxopentyl)‐1‐isochromenones were isolated regardless of the reaction conditions.     

Reaction of N‐(phenyl and methyl)‐C‐arylnitrones with DMAD in ionic liquid: Efficient synthesis of Δ4‐isoxazolines

Facile synthesis of N‐(methyl and phenyl)‐Δ⁴‐isoxazolines via the reaction of (Z)‐N‐(methyl and phenyl)‐C‐arylnitrones with dimethyl acethylenedicarboxylate, DMAD, in ionic liquid is described. (Z)‐N‐methyl‐C‐arylnitrones afforded the high yield of N‐methyl‐Δ⁴‐isoxazolines 4a , 4b , 4c , 4d , 4e in ionic liquid, [bmim]BF₄, at room temperature. However, the reaction of (Z)‐N‐phenyl‐C‐arylnitrones with DMAD afforded the mixtures of cis and trans isomers of related N‐phenyl‐Δ⁴‐isoxazolines ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j ) under these conditions. J. Heterocyclic Chem., (2012).     

Synthesis of Pyrano‐ and Pyrido‐Anellated Pyranosides as Precursors for Nucleoside Analogues

The push‐pull activated methyl (3Z)‐4,6‐O‐benzylidene‐3‐[(methylthio)methylene]‐3‐deoxy‐α‐D‐erythro‐hexopyranosid‐2‐ulose (1) reacted with dialkyl malonate in the presence of potassium carbonate to give the alkyl (2R,4aR,6S,10bS)‐4a,6,8,10b‐tetrahydro‐6‐methoxy‐8‐oxo‐2‐phenyl‐4H‐pyrano[3′,2′:4,5]pyrano[3,2‐d][1,3]dioxine‐9‐carboxylates 2 and 3. Treatment of 1 with 3‐oxo‐N‐phenyl‐butyramide, N‐(4‐methoxy‐phenyl)‐3‐oxo‐butyramide, and 3‐oxo‐N‐o‐tolyl‐butyramide, respectively, in the presence of potassium carbonate and 18‐crown‐6 yielded the (2R,4aR,6S,10bS)‐9‐acetyl‐7‐aryl‐4,4a,7,10b‐tetrahydro‐6‐methoxy‐2‐phenyl[1,3]dioxino‐[4′,5′:5,6]pyrano[3,4‐b]pyridin‐8(6H)‐ones 4–6. (2R,4aR,6S,10bS)‐4,4a,8,10b‐Tetrahydro‐6‐methoxy‐8‐oxo‐2‐phenyl‐4H‐pyrano[3′,2′:4,5]pyrano[3,2‐d][1,3]dioxine‐9‐carboxamide (7) was prepared by anellation reactions of 1 either with malononitrile or with cyanoacetamide.     

Four tri­fluoro­methyl­nitro­benzene analogues

The crystal structures of four tri­fluoro­methyl­nitro­benzene analogues (CF₃)C₆H₃(NO₂)[C₄H₈N₂]R (where C₄H₈N₂ is piperazinyl and R is ethyl carboxyl­ate, CO₂C₂H₅, or phenyl, C₆H₅), have been determined, and their conformations and packing arrangements are compared. The four compounds are ethyl 4‐[4‐nitro‐2‐(tri­fluoro­methyl)­phenyl]­piperazine‐1‐car­boxyl­ate, (I), and ethyl 4‐[2‐nitro‐4‐(tri­fluoro­methyl)­phen­yl]piper­azine‐1‐carboxyl­ate, (II), both C₁₄H₁₆F₃N₃O₄, and 1‐­[4‐nitro‐2‐(tri­fluoro­methyl)­phenyl]‐4‐phenyl­piperazine, (III), and 1‐[2‐nitro‐4‐(tri­fluoro­methyl)­phenyl]‐4‐phenyl­piperazine, (IV), both C₁₇H₁₆F₃N₃O₂. All mol­ecules adopt a rod‐like conformation, while the asymmetric units of (II) and (IV) contain two unique mol­ecules that pack as monodirectional pairs. All mol­ecules pack with C—H⋯O/F close contacts to all but one of the O atoms and to five of the 18 F atoms.     

Synthesis and antimicrobial activity of tris phosphonates

Syntheses of novel [{(3‐dialkoxy‐phosphoryl)‐(substituted‐phenyl‐methyl)‐2‐oxo‐2‐phenyl‐2,3‐dihydro‐2λ⁵–benzo [1,3,2] diazaphosphol‐1‐yl}‐(substituted‐phenyl)‐methyl]‐phosphonic acid diethyl/dimethyl esters ( 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j ) were conveniently accomplished by cyclocondensation of [(2‐{(dimethoxy‐phosphoryl)‐phenyl‐methyl)‐amino}‐phenyl amino)‐phenyl‐methyl]phosphonic acid diethyl/dimethyl esters ( 2a , 2b , 2c , 2d , 2e , 2f , 2g , 2h , 2i , 2j ) with phenyl phosphonic dichloride in dry toluene in the presence of triethylamine at 40°C. The title compounds were characterized by physicospectral techniques. All the synthesized compounds were found to possess antimicrobial properties. J. Heterocyclic Chem., 2011.     

An Efficient Method for the Synthesis of Laquinimod

Laquinimod, 5‐chloro‐1,2‐dihydro‐N‐ethyl‐4‐hydroxy‐1‐methyl‐2‐oxo‐N‐ phenyl‐3‐quinoline carboxamide, is an oral drug in clinical trials for the treatment of multiple sclerosis. An efficient synthetic method for laquinimod from 2‐amino‐6‐chlorobenzoic acid via four steps was established. The overall yield of laquinimod is up to 82% as compared with 70% reported in literature. It has also been demonstrated that green reagent dimethyl carbonate is not suitable for the N‐methylation of 5‐chloroisatoic anhydride owing to the ring‐cleavage reaction induced by the generated methanol. The ring‐cleavage by‐products were isolated and characterized by ¹H‐NMR and ¹³C‐NMR. In addition, in the study of laquinimod derivatives, we found that 5‐chloro‐1,2‐dihydro‐N‐ethyl‐4‐hydroxy‐1‐methyl‐2‐oxo‐N‐phenyl‐3‐quinoline carboxamide (laquinimod) was obtained in much higher yield than 7‐chloro‐1,2‐dihydro‐N‐ethyl‐4‐hydroxy‐1‐methyl‐2‐oxo‐N‐phenyl‐3‐quinoline carboxamide under the same reaction conditions, and it is possibly attributed to a neighboring group effect.     

Synthesis and Heterocyclization of 1‐Aryl‐2‐methyl‐4‐oxo‐1,4,5,6‐tetrahydropyridine‐3‐carboxylates

A series of novel isoxazole, dihydropyrazolone, and tetrahydropyridine derivatives were synthesized by the reaction of corresponding ethyl 1‐substituted aryl‐2‐methyl‐4‐oxo‐1,4,5,6‐tetrahydropyridine‐3‐carboxylates with different hydrazines and hydroxylamine. Reaction of tetrahydropyridone with N ,N‐dimethylformamide dimethyl acetal provided 1‐(5‐chloro‐2‐methylphenyl)‐2‐[2‐(dimethylamino)ethenyl]‐4‐oxo‐1,4,5,6‐tetrahydropyridine‐3‐carboxylate, which was cyclized into a bicyclic compound on treatment with ammonium acetate. The structures of all synthesized compounds were confirmed by IR, ¹H NMR, and ¹³C NMR spectroscopy data. The structure of 5‐(5‐chloro‐2‐methylphenyl)‐4‐methyl‐2‐phenyl‐2,5,6,7‐tetrahydro‐3H‐pyrazolo[4,3‐c]pyridin‐3‐one was unambiguously assigned by means of X‐ray analysis data.     

Preparation of 1‐substituted‐5‐[(2‐oxo‐2‐phenyl)ethyl]imidazoles

New high yield preparation methods were developed for the pharmaceutically interesting compounds, 1‐benzyl‐, 1‐methyl‐, and 1H‐5‐[(2‐oxo‐2‐phenyl)ethyl]imidazoles 1a‐c , respectively. The title compounds were synthesized by four different methods using various starting materials. Two of the methods involved transformation reactions of the key intermediates, 1‐substituted‐5‐[(2‐nitro‐2‐phenyl)ethenyl]imidazoles 2a‐c and 1‐substituted‐5‐[(2‐nitro‐2‐phenyl)ethyl]imidazoles 3a‐c , while the other two utilized the oxidation of 1‐substituted‐5‐[(2‐hydroxy‐2‐phenyl)ethyl]imidazoles 4a‐c , with chromic oxide, and the umpolung reaction of benzaldehyde followed by a condensation reaction of the umpolung intermediate with imidazolecarboxaldehydes 6a‐c.     

Ranitidine hydro­chloride,a polymorphic crystal form

In the title compound, di­methyl­({5‐[2‐(1‐methyl­amino‐2‐nitro­eth­enyl­amino)­ethyl­thio­methyl]‐2‐furyl}­methyl)­ammon­ium chloride, C₁₃H₂₃N₄O₃S⁺·­Cl^?, protonation occurs at the di­methyl­amino N atom. The ranitidine mol­ecule adopts an eclipsed conformation. Bond lengths indicate extensive electron delocalization in the N,N′‐di­methyl‐2‐nitro‐1,1‐ethenedi­amine system of the mol­ecule. The nitro and methyl­amino groups are trans across the side chain C=C double bond, while the ethyl­amino and nitro groups are cis. The Cl^? ions link mol­ecules through hydrogen bonds.     

Synthesis of tetracyclic system of 2,4‐di(tert‐butyl)‐6,7‐dihydrofuro[2′,3′:3,4]cyclohepta[1,2‐b]indole

For the first time, tetracyclic compounds, namely, furo[2′,3′:3,4]cyclohepta[1,2‐b]indoles were synthesized by recyclization of ortho‐substituted aryldifurylmethanes containing tert‐butyl groups at C5 positions of the furan rings. It was shown that [2‐(benzoylamino)phenyl]bis(5‐tert‐butyl‐2‐furyl)methanes 12 are transformed into tetracycles 15 at room temperature under treatment with POCl₃ in benzene solution containing some drops of water. The reaction proceeds via the intermediate formation of 1‐benzoylamino‐3‐(5‐tert‐butyl‐2‐furyl)‐2‐(4,4‐dimethyl‐3‐oxopentyl)indoles 14 which can be isolated from the reaction mixture. The method is very simple but its application is restricted due to side reactions if electron‐releasing groups are present in 12 . On the other hand, the decrease of electron density on furan ring in the starting compounds (for example, the use of [2‐X‐phenyl]difurylmethanes (where X = tosylamino or hydroxy group) prevents cyclization under the studied reaction conditions. As a result, corresponding ketones are formed as products of recyclization. J. Heterocyclic Chem., (2011).     

Cyano–cyano and chloro–cyano interactions in two imidazole derivatives

In two closely related 1‐aryl‐2‐methyl‐4‐nitro‐5‐cyano­imid­azoles, namely 2‐methyl‐4‐nitro‐1‐phenyl‐1H‐imidazole‐5‐carbo­nitrile, C₁₁H₈N₄O₂, and 1‐(4‐chloro­phenyl)‐2‐methyl‐4‐nitro‐1H‐imidazole‐5‐carbo­nitrile, C₁₁H₇ClN₄O₂, different weak intermolecular interactions determine the crystal packing. In the 1‐phenyl derivative, dipole–dipole interactions between antiparallel cyano groups connect mol­ecules into centrosymmetric dimers, while in the 1‐(4‐chloro­phenyl) derivative, the dimers are connected by C≡N⋯Cl—C halogen bonds. These interactions, together with weak C—H⋯O(N) hydrogen bonds, connect mol­ecules related by subsequent centres of inversion into infinite tapes.     

Organic Base‐Catalyzed Stereoselective Isomerizations of 4‐Hydroxy‐4‐phenyl‐but‐2‐ynoic Acid Methyl Ester to (E)‐ and (Z)‐4‐Oxo‐4‐phenyl‐but‐2‐enoic Acid Methyl Esters

We have developed a 1,4‐diazabicyclo[2.2.2]octane (DABCO)‐catalyzed isomerization of 4‐hydroxy‐4‐phenyl‐but‐2‐ynoic acid methyl ester to (E)‐4‐oxo‐4‐phenyl‐but‐2‐enoic acid methyl ester and an N,N‐diisopropylethylamine‐catalyzed isomerization of the same substrate to (Z)‐4‐oxo‐4‐phenyl‐but‐2‐enoic acid methyl ester.     

Packing considerations of bis‐dimedone derivatives

We have determined the crystal structures of 2,2′‐(4‐fluoro­phenyl)­methyl­enebis(3‐hydroxy‐5,5‐di­methyl‐2‐cyclo­hexen‐1‐one), C₂₃H₂₇FO₄, (I), 2,2′‐(4‐chloro­phenyl)­methyl­enebis(3‐hy­droxy‐5,5‐dimethyl‐2‐cyclo­hexen‐1‐one), C₂₃H₂₇ClO₄, (II), 2,2′‐(4‐hydroxy­phenyl)­methyl­enebis(3‐hydroxy‐5,5‐di­methyl‐2‐cyclo­hexen‐1‐one), C₂₃H₂₈O₅, (III), 2,2′‐(4‐methyl­phenyl)­methyl­enebis(3‐hydroxy‐5,5‐di­methyl‐2‐cyclo­hexen‐1‐one), C₂₄H₃₀O₄, (IV), 2,2′‐(4‐methoxy­phenyl)­methyl­enebis(3‐hy­droxy‐5,5‐di­methyl‐2‐cyclo­hexen‐1‐one), C₂₄H₃₀O₅, (V), and 2,2′‐(4‐N,N′‐di­methyl­amino­phenyl)­methyl­enebis(3‐hydroxy‐5,5‐di­methyl‐2‐cyclo­hexen‐1‐one), C₂₅H₃₃NO₄, (VI). Structures (III) to (VI) of these bis‐dimedone derivatives show nearly the same packing pattern irrespective of the different substituent in the para position of the aromatic ring. However, (II) does not fit into this scheme, although the Cl atom is a substituent not too different from the others. The different packing of the fluoro compound, (I), can be explained by the fact that it crystallizes with two mol­ecules in the asymmetric unit, which show a different conformation of the dimedone ring. On the other hand, (I) shows a similar packing pattern to bis(2‐hydroxy‐4,4‐di­methyl‐6‐oxo‐1‐cyclo­hexenyl)­phenyl­methane, a compound containing an aromatic ring without any substituent and with Z′ = 2.     

Different molecular conformations co‐exist in each of three 2‐aryl‐N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)acetamides: hydrogen bonding in zero,one and two dimensions

4‐Antipyrine [4‐amino‐1,5‐dimethyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐one] and its derivatives exhibit a range of biological activities, including analgesic, antibacterial and anti‐inflammatory, and new examples are always of potential interest and value. 2‐(4‐Chlorophenyl)‐N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)acetamide, C₁₉H₁₈ClN₃O₂, (I), crystallizes with Z′ = 2 in the space group P, whereas its positional isomer 2‐(2‐chlorophenyl)‐N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)acetamide, (II), crystallizes with Z′ = 1 in the space group C2/c; the molecules of (II) are disordered over two sets of atomic sites having occupancies of 0.6020 (18) and 0.3980 (18). The two independent molecules of (I) adopt different molecular conformations, as do the two disorder components in (II), where the 2‐chlorophenyl substituents adopt different orientations. The molecules of (I) are linked by a combination of N—H…O and C—H…O hydrogen bonds to form centrosymmetric four‐molecule aggregates, while those of (II) are linked by the same types of hydrogen bonds forming sheets. The related compound N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)‐2‐(3‐methoxyphenyl)acetamide, C₂₀H₂₁N₃O₃, (III), is isomorphous with (I) but not strictly isostructural; again the two independent molecules adopt different molecular conformations, and the molecules are linked by N—H…O and C—H…O hydrogen bonds to form ribbons. Comparisons are made with some related structures, indicating that a hydrogen‐bonded R₂²(10) ring is the common structural motif.     

Utility of Enaminonitriles in Heterocyclic Synthesis: Synthesis of Some New Pyrazole,Pyridine, and Pyrimidine Derivatives

The starting (1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)carbonohydrazonoyl dicyanide ( 2 ) was used as key intermediate for the synthesis of 3‐amino‐2‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐ylazo)‐[3‐substituted]‐1‐yl‐acrylonitrile derivatives ( 3 – 10 ). In addition, nitrile derivative 2 reacted with hydrazine hydrate or malononitrile to afford the corresponding 3,5‐diaminopyrazole 11 and enaminonitrile derivative 13 , respectively. On the other hand, compound 3 was subjected to react with malononitrile, acetic anhydride, triethylorthoformate, N,N‐dimethylformamide (DMF)‐dimethylacetal, thiourea, and hydroxylamine hydrchloride to afford antipyrine derivatives 16 – 21 . Moreover, the reaction of enaminonitrile 3 with carbon disulfide in pyridine afforded the pyrimidine derivative 22 , whereas, in NaOH/DMF followed by the addition of dimethyl sulphate afforded methyl carbonodithioate 24 . The reaction of enaminonitrile derivatives 3 – 5 with phenylisothiocyanate afforded the thiopyrimidine derivatives 25a – c . Finally, the enaminonitrile 4 reacted with 3‐(4‐chloro‐phenyl)‐1‐phenyl‐propenone to afford the pyridine derivative 27 . The newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹³C‐NMR, ¹H–NMR, and MS).     

Reduced 3,4′‐bipyrazoles from a simple pyrazole precursor: synthetic sequence,molecular structures and supramolecular assembly

The reaction of 5‐chloro‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde and N‐benzylmethylamine under microwave irradiation gives 5‐[benzyl(methyl)amino]‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde, C₁₉H₁₉N₃O, (I). Subsequent reactions under basic conditions, between (I) and a range of acetophenones, yield the corresponding chalcones. These undergo cyclocondensation reactions with hydrazine to produce reduced bipyrazoles which can be N‐formylated with formic acid or N‐acetylated with acetic anhydride. The structures of (I) and of representative examples from this reaction sequence are reported, namely the chalcone (E )‐3‐{5‐[benzyl(methyl)amino]‐3‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl}‐1‐(4‐bromophenyl)prop‐2‐en‐1‐one, C₂₇H₂₄BrN₃O, (II), the N‐formyl derivative (3RS )‐5′‐[benzyl(methyl)amino]‐3′‐methyl‐1′,5‐diphenyl‐3,4‐dihydro‐1′H ,2H‐[3,4′‐bipyrazole]‐2‐carbaldehyde, C₂₈H₂₇N₅O, (III), and the N‐acetyl derivative (3RS )‐2‐acetyl‐5′‐[benzyl(methyl)amino]‐5‐(4‐methoxyphenyl)‐3′‐methyl‐1′‐phenyl‐3,4‐dihydro‐1′H ,2H‐[3,4′‐bipyrazole], which crystallizes as the ethanol 0.945‐solvate, C₃₀H₃₁N₅O₂·0.945C₂H₆O, (IV). There is significant delocalization of charge from the benzyl(methyl)amino substituent onto the carbonyl group in (I), but not in (II). In each of (III) and (IV), the reduced pyrazole ring is modestly puckered into an envelope conformation. The molecules of (I) are linked by a combination of C—H…N and C—H…π(arene) hydrogen bonds to form a simple chain of rings; those of (III) are linked by a combination of C—H…O and C—H…N hydrogen bonds to form sheets of R ²₂(8) and R ⁶₆(42) rings, and those of (IV) are linked by a combination of O—H…N and C—H…O hydrogen bonds to form a ribbon of edge‐fused R ²₄(16) and R ⁴₄(24) rings.     

An oxazol‐5(4H)‐one from benzyloxy­carbonyl‐(Aib)4‐OH

Benzyl N‐[8‐(4,4‐dimethyl‐5‐oxo‐4,5‐dihydrooxazol‐2‐yl)‐2,5,5,8‐tetra­methyl‐3,6‐dioxo‐4,7‐diazanon‐2‐yl]­carbamate, C₂₄H₃₄N₄O₆, an oxazol‐5(4H)‐one from N‐α‐benzyloxycarbonyl‐(Aib)₄‐OH (Aib = α‐amino­isobutyryl) represents the longest peptide oxazolone so far characterized by X‐ray diffraction. The overall geometry of the oxazolone ring compares well with literature data. The Aib(1) and Aib(2) residues are folded into a type III β‐bend, while the conformation adopted by Aib(3), preceding the oxazolone moiety, is semi‐extended. The disposition of the oxazolone ring relative to the preceding residue is stabilized by C—­H?N and C—H?O intramolecular interactions.