2,2‐Dimethyl‐5‐nitroso‐1,3‐dioxan‐5‐yl benzoate, 2,2‐dimethyl‐5‐nitroso‐1,3‐dioxan‐5‐yl 4‐chlorobenzoate and 5‐nitroso‐1,3‐dioxan‐5‐yl 4‐chlorobenzoate

The crystal structures of 2,2‐dimethyl‐5‐nitroso‐1,3‐dioxan‐5‐yl benzoate, C₁₃H₁₅NO₅, (I), 2,2‐dimethyl‐5‐nitroso‐1,3‐dioxan‐5‐yl 4‐chlorobenzoate, C₁₃H₁₄ClNO₅, (II), and 5‐nitroso‐1,3‐dioxan‐5‐yl 4‐chlorobenzoate, C₁₁H₁₁NO₅, (III), have been determined in order to gain insight into the conformational preference of α‐benzoyloxynitroso. Unfavourable 1,3‐diaxial interactions force (I) and (II) to crystallize in the 2,5 twist‐boat conformation, whereas compound (III), lacking this destabilizing interaction, crystallizes in the chair conformation.     

Syntheses of 4‐(5‐oxo‐1,2,4‐triazol‐3‐yl)‐sydnones and 4‐(4‐arylamino‐5‐oxo‐1,2,4‐triazol‐3‐yl)‐sydnones from Sydnone Derivatives and Their Fragments

4‐(5‐oxo‐1,2,4‐triazol‐3‐yl)‐sydnones 11 and 4‐(4‐arylamino‐5‐oxo‐1,2,4‐triazol‐3‐yl)‐sydnones 13 have been obtained from a‐chloroformylarylhydrazine hydrochloride 2 . Moreover, the intermediates, including 3, 4 , 9 and 10 , in this study are synthetically informative and valuable. It is also noteworthy that three reactants, 1, 2 and sydnonecarbaldehydes, were prepared from sydnone derivatives and their fragments. The oxidative cyclizations of sydnonecarbaldehyde semicarbazones 9 and carbazones 10 with two different oxidizing agents (Cu(ClO₄)₂ and Fe(ClO₄)₃) have been extensively examined. The reaction time and the yields of cyclizations were affected by the substituents of semicarbazones 9 and carbazones 10.     

Reaction of Ketene Dithioacetals with Pyrazolylcarbohydrazide： Synthesis and Biological Activities of Ethyl 5-Amino-1-（5＇-methyl-1 ＇-t-butyl-4＇-pyrazolyl）carbonyl-3-methylthio-1 H-pyrazole-4-carboxylate

The title compound, C16H23N5O3S, ethyl 5-amino-1-(5‘-methyl-1‘-t-butyl-4‘-pyrazolyl)carbonyl-3-methylthio-1H-pyrazole-4-carboxylate (5) has been synthesized by the treatment of ethyl 2-cyano-3,3-dimethylthioacrylate with 1-t-butyl-5-methyl-4-hydrazinocarbonylpyrazole (4) in refluxed ethanol. The possible mechanism of the above reaction was also discussed. The results of biological test show that the title compound has fungicidal and plant growth regulation activities.     

Polymorphism of 3‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐yl)‐ and 3‐[5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl]‐2H‐chromen‐2‐ones

This study of 3‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐yl)‐2H‐chromen‐2‐one, C₁₇H₁₀N₂O₃, 1 , and 3‐[5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl]‐2H‐chromen‐2‐one, C₁₆H₉N₃O₃, 2 , was performed on the assumption of the potential anticancer activity of the compounds. Three polymorphic structures for 1 and two polymorphic structures for 2 have been studied thoroughly. The strongest intermolecular interaction is stacking of the `head‐to‐head' type in all the studied crystals. The polymorphic structures of 1 differ with respect to the intermolecular interactions between stacked columns. Two of the polymorphs have a columnar or double columnar type of crystal organization, while the third polymorphic structure can be classified as columnar‐layered. The difference between the two structures of 2 is less pronounced. Both crystals can be considered as having very similar arrangements of neighbouring columns. The formation of polymorphic modifications is caused by a subtle balance of very weak intermolecular interactions and packing differences can be identified only using an analysis based on a study of the pairwise interaction energies.     

Formation of α‐SF5‐Enolate Enables Preparation of 3‐SF5‐Quinolin‐2‐ones, 3‐SF5‐Quinolines,and 3‐SF5‐Pyridin‐2‐ones: Evaluation of their Physicochemical Properties

This study describes, for the first time, the generation of a SF₅‐substituted ester enolate from benzyl SF₅‐acetate under soft enolization conditions, which in turn participates in aldol addition reactions in high yield. The reaction was applied in the synthesis of 3‐SF₅‐quinolin‐2‐ones, 3‐SF₅‐quinolines, and 3‐SF₅‐pyridin‐2‐ones, none of which have previously been reported. To provide guidelines for their use in drug discovery, the physicochemical properties of these building blocks were determined and compared with those of their CF₃‐ and t‐Bu‐analogues.     

Formation of α‐SF5‐Enolate Enables Preparation of 3‐SF5‐Quinolin‐2‐ones, 3‐SF5‐Quinolines,and 3‐SF5‐Pyridin‐2‐ones: Evaluation of their Physicochemical Properties

This study describes, for the first time, the generation of a SF₅‐substituted ester enolate from benzyl SF₅‐acetate under soft enolization conditions, which in turn participates in aldol addition reactions in high yield. The reaction was applied in the synthesis of 3‐SF₅‐quinolin‐2‐ones, 3‐SF₅‐quinolines, and 3‐SF₅‐pyridin‐2‐ones, none of which have previously been reported. To provide guidelines for their use in drug discovery, the physicochemical properties of these building blocks were determined and compared with those of their CF₃‐ and t‐Bu‐analogues.     

One‐Pot Synthesis of Pyrrolo[1,2‐a]quinolin‐1‐ones by the Cyclocondensation of 5‐Hydroxy‐1‐arylpyrrolidin‐2‐ones with Dicarbonyls

A one‐pot synthesis of pyrrolo[1,2‐a]quinolin‐1‐ones has been developed from the reactions of 5‐hydroxy‐1‐arylpyrrolidin‐2‐ones with 1,3‐dicarbonyl compounds under the promotion of H₃PO₄/P₂O₅ or HOAc/H₂SO₄. The pyrrolo[1,2‐a]quinolin‐1‐ones are formed by two‐step reactions, that is, the coupling of N‐acyliminium ion intermediates produced from 5‐hydroxy‐1‐arylpyrrolidin‐2‐ones with 1,3‐dicarbonyls and subsequent Friedel–Crafts reactions of the resulting ketone with the aryl ring.     

Synthesis of 5‐[2‐(guanin‐9‐yl)‐ and 5‐[2‐(2‐aminopurin‐9‐yl)ethyl]‐2‐D‐ribo‐(1,2′,3′,4′‐tetrahydroxybutyl)‐1,3‐dioxane

Stereoselective synthesis of 5‐[2‐(guanin‐9‐yl)‐ and 5‐[2‐(2‐aminopurin‐9‐yl)ethyl]‐2‐D‐ribo‐(1′,2′,3′,4′‐tetrahydroxybutyl)‐1,3‐dioxane, 2‐5, as potential prodrugs of penciclovir, has been accomplished in six steps from readily available 2,3,4,5‐tetra‐O‐acetyl‐aldehydo‐D‐ribose ( 6 ) and the 1,3‐diol 7 . It has been demonstrated that the use of boron trifluoride diethyl etherate (BF₃·Et₂O) in dichloromethane along with excess anhydrous copper(II) sulfate was crucial for the efficient formation of cyclic acetal 8 . In addition, the chromatographic separation of cis and trans isomers of the cyclic acetal at the bromide stage 10 was feasible, which was requisite for the successful stereoselective synthesis of the ribosyl derivatives 2–5 .     

Copper‐catalyzed Synthesis of N‐alkylated 2‐(4‐substituted‐1H‐1,2,3‐triazol‐1‐yl)‐1H‐indole‐3‐carbaldehyde by Step‐wise and One‐pot Three‐component Huisgen's 1,3‐dipolar Cycloaddition Reaction

An efficient method for the synthesis of N‐alkylated 2‐(4‐substituted‐1H‐1,2,3‐triazol‐1‐yl)‐1H‐indole‐3‐carbaldehyde has been developed starting from oxindole and indole using Huisgen's 1,3‐dipolar cycloaddition reaction of organic azides to alkynes. The effect of catalysts and solvent on these reactions has been investigated. Among all these conditions, while using CuSO₄·5H₂O, DMF was found to be the best system for this reaction. It could also be prepared in a one‐pot three‐component manner by treating equimolar quantities of halides, azides, and alkynes. The Huisgen's 1,3‐dipolar cycloaddition reaction was performed using CuSO₄·5H₂O in DMF with easy work‐up procedure.     

7‐Iodo‐8‐aza‐7‐deaza‐2′‐deoxy­adenosine and 7‐bromo‐8‐aza‐7‐deaza‐2′‐deoxyadenosine

The isomorphous structures of the title molecules, 4‐amino‐1‐(2‐deoxy‐β‐d ‐erythro‐pento­furan­osyl)‐3‐iodo‐1H‐pyrazolo‐[3,4‐d]pyrimidine, (I), C₁₀H₁₂IN₅O₃, and 4‐amino‐3‐bromo‐1‐(2‐deoxy‐β‐d ‐erythro‐pento­furan­osyl)‐1H‐pyrazolo[3,4‐d]­pyrimidine, (II), C₁₀H₁₂BrN₅O₃, have been determined. The sugar puckering of both compounds is C1′‐endo (^1′E). The N‐­glycosidic bond torsion angle χ¹ is in the high‐anti range [?73.2 (4)° for (I) and ?74.1 (4)° for (II)] and the crystal structure is stabilized by hydrogen bonds.     

Regiodirected Synthesis and Stereochemistry of 2,4,8‐Trialkyl‐3‐thia‐1,5‐diazabicyclo[3.2.1]octanes and α,ω‐Bis(2,4,6‐trialkyl‐1,3,5‐dithiazinane‐5‐yl)alkanes

2,4,8‐Trialkyl‐3‐thia‐1,5‐diazabicyclo[3.2.1]octanes have been obtained by the regioselective and stereoselective cyclocondensation of 1,2‐ethanediamine with aldehydes RCHO (R═Me, Et, Prⁿ, Buⁿ, Pentⁿ) and H₂S at molar ratio 1:3:2 at 0°C. The increase in molar ratio of thiomethylation mixture RCHO–H₂S (6:4) at 40°C resulted in selective formation of bis‐(2,4,6‐trialkyl‐1,3,5‐dithiazinane‐5‐yl)ethanes. Cyclothiomethylation of aliphatic α,ω‐diamines with aldehydes RCHO (R═Me, Et) and H₂S at molar ratio 1:6:4 and at 40°С led to α,ω‐bis(2,4,6‐trialkyl‐1,3,5‐dithiazinane‐5‐yl)alkanes. Stereochemistry of 2,4,8‐trialkyl‐3‐thia‐1,5‐diazabicyclo[3.2.1]octanes have been determined by means of ¹H and ¹³С NMR spectroscopy and further supported by DFT calculations at the B3LYP/6‐31G(d,p) level. The structure of α,ω‐bis(2,4,6‐trialkyl‐1,3,5‐dithiazinane‐5‐yl)alkanes was confirmed by single‐crystal X‐ray diffraction study.     

1‐Acetyl‐3‐ferrocenyl‐5‐methyl‐1H‐pyrazole and 1‐acetyl‐5‐ferrocenyl‐3‐(2‐pyrid­yl)‐1H‐pyrazole

Mol­ecules of 1‐acetyl‐3‐ferrocenyl‐5‐methyl‐1H‐pyrazole, [Fe(C₅H₅)(C₁₁H₁₁N₂O)], form a centrosymmetric dimer generated by a combination of one C—H⋯π(pyrazole) and one C—H⋯π(cyclo­penta­dienyl) inter­action. The dimers are linked by C—H⋯π inter­actions, involving the pyrazole rings as acceptors, into layers parallel to (10). Mol­ecules of 1‐acetyl‐5‐ferrocenyl‐3‐(2‐pyrid­yl)‐1H‐pyrazole, [Fe(C₅H₅)(C₁₅H₁₂N₃O)], are linked by C—H⋯O inter­actions into a chain running in the [010] direction. Two chains of this type passing through each unit cell are connected by O⋯π(pyridyl) inter­actions into an [010] double chain.     

Synthesis of 4‐Aryl‐1,7‐naphthyridine‐2(1H)‐thiones by the Electrocyclic Reaction of 4‐(1‐Arylalk‐1‐enyl)‐3‐isothiocyanatopyridines Generated in situ from the Corresponding Isocyanides

A convenient synthis for 4‐substituted and 3,4‐disubstituted 1,7‐naphthyridine‐2(1H)‐thiones 7 has been developed. The method is based on the electrocyclic reaction of 4‐(1‐arylalk‐1‐enyl)‐3‐isothiocyanatopyridines 6 , generated in situ by the treatment of the respective isocyanides 5 with S₈ in the presence of a catalytic amount of selenium. The isocyanides 5 can be easily prepared from commercially available pyridin‐3‐amine by conventional organic reactions.     

Synthesis of Some Novel Phenyl Substituted Oxothiazolidin- 1’’,3’’,4’’-thiadiazolo-[3’,4’-b]thiazoline of 3β-Substituted Cholestane

Three title compounds 4a—4c have been synthesized by the cyclodehydration of 1’-benzylidine-4’-(3β-substituted-5α-cholestane-6-yl)thiosemicarbazones 2a—2c with thioglycolic acid followed by the treatment with cold conc. H2SO4 in dioxane. The compounds 2a—2c were prepared by condensation of 3β-substituted-5α-cholestan- 6-one-thiosemicarbazones 1a—1c with benzaldehyde. These thiosemicarbazones 1a—1c were obtained by the reaction of corresponding 3β-substituted-5α-cholestan-6-ones with thiosemicarbazide in the presence of few drops of conc. HCl in methanol. The structures of the products have been established on the basis of their elemental, analytical and spectral data.     

New Synthesis and Reactions of Ethyl 5‐amino‐4‐cyano‐1‐phenyl‐1H‐pyrazole‐3‐carboxylate

Synthesis of ethyl 5‐amino‐4‐cyano‐1‐phenyl‐1H‐pyrazole‐3‐carboxylate 5 has been achieved via abnormal Beckmann rearrangement of o‐chloroaldehyde 1 . Reaction of o‐aminocarbonitrile 5 with concentrated H₂SO₄ furnished expected o‐aminocarboxamide pyrazole 6 . Key intermediates o‐aminocarbonitrile 5 and o‐aminocarboxamide 6 were successfully utilized for the synthesis of pyrazolopyrimidine derivatives. The replacement of Cl in o‐chlorocarbonitrile 3 with secondary amine furnished new synthon 13 , which was further used for the synthesis of polysubstituted heterocycles. The obtained new products were well characterized by IR, ¹H and ¹³C NMR, and mass spectra.     

Proton‐transfer compounds of 8‐hydroxy‐7‐iodoquinoline‐5‐sulfonic acid (ferron) with 4‐chloroaniline and 4‐bromoaniline

The crystal structures of the proton‐transfer compounds of ferron (8‐hydroxy‐7‐iodoquinoline‐5‐sulfonic acid) with 4‐chloroaniline and 4‐bromoaniline, namely 4‐chloroanilinium 8‐hydroxy‐7‐iodoquinoline‐5‐sulfonate monohydrate, C₆H₇ClN⁺·C₉H₅INO₄S⁻·H₂O, and 4‐bromoanilinium 8‐hydroxy‐7‐iodoquinoline‐5‐sulfonate monohydrate, C₆H₇BrN⁺·C₉H₅INO₄S⁻·H₂O, have been determined. The compounds are isomorphous and comprise sheets of hydrogen‐bonded cations, anions and water molecules which are extended into a three‐dimensional framework structure through centrosymmetric R₂²(10) O—H...N hydrogen‐bonded ferron dimer interactions.     

The diastereoisomers methyl 5‐(S)‐[2‐(R)/(S)‐methoxycarbonyl)‐2,3,4,5‐tetrahydropyrrol‐1‐ylcarbonyl]‐1‐(4‐methylphenyl)‐4,5‐dihydropyrazole‐3‐carboxylate

The title diastereoisomers, methyl 5‐(S)‐[2‐(S)‐methoxy­carbonyl)‐2,3,4,5‐tetra­hydro­pyrrol‐1‐yl­carbonyl]‐1‐(4‐methyl­phenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxyl­ate and methyl 5‐(S)‐[2‐(R)‐methoxycarbonyl)‐2,3,4,5‐tetrahydropyrrol‐1‐ylcarbonyl]‐1‐(4‐methyl­phenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxylate, both C₁₉H₂₃N₃O₅, have been studied in two crystalline forms. The first form, methyl 5‐(S)‐[2‐(S)‐methoxy­carbonyl)‐2,3,4,5‐tetrahydropyrrol‐1‐ylcarbonyl]‐1‐(4‐methylphenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxyl­ate–methyl 5‐(S)‐[2‐(R)‐methoxy­carbonyl)‐2,3,4,5‐tetra­hydro­pyrrol‐1‐yl­carbonyl]‐1‐(4‐methylphenyl)‐4,5‐dihydropyrazole‐3‐carboxylate (1/1), 2(S),5(S)‐C₁₉H₂₃N₃O₅·2(R),5(S)‐C₁₉H₂₃N₃O₅, contains both S,S and S,R isomers, while the second, methyl 5‐(S)‐[2‐(S)‐methoxycarbonyl)‐2,3,4,5‐tetrahydro­pyrrol‐1‐ylcarbonyl]‐1‐(4‐methyl­phenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxyl­ate, 2(S),5(S)‐C₁₉H₂₃N₃O₅, is the pure S,S isomer. The S,S isomers in the two structures show very similar geometries, the maximum difference being about 15° on one torsion angle. The differences between the S,S and S,R isomers, apart from those due to the inversion of one chiral centre, are more remarkable, and are partially due to a possible rotational disorder of the 2‐­(methoxycarbonyl)tetrahydropyrrole group.     

Synthesis,Characterization, and Crystal Structure of 1,3‐Dipentafluorophenyl‐2,2,2,4,4,4‐hexazido‐1,3‐diaza‐2,4‐diphosphetidine

1,3‐Dipentafluorophenyl‐2,2,2,4,4,4‐hexazido‐1,3‐diaza‐2,4‐diphosphetidine ( 1 ) was synthesized by the reaction of [(C₆F₅)NPCl₃]₂ with trimethylsilyl azide in CH₂Cl₂ and characterized by multinuclear NMR and vibrational spectroscopy. The molecular structure of the compound was determined by single‐crystal X‐ray structure analysis. [(C₆F₅)NP(N₃)₃]₂ crystallizes in the monoclinic space group P2₁/n with a = 9.6414(2), b = 7.4170(1) and c = 15.9447(4) Å, β = 94.4374(9)°, with 2 formula units per unit cell. The bond situation in [(C₆F₅)NP(N₃)₃]₂ has been studied on the basis of NBO analysis. The antisymmetric stretching vibration of the azide groups is discussed. The structural diversity of 1 and 1,3‐diphenyl‐2,2,2,4,4,4‐hexazido‐1,3‐diaza‐2,4‐diphosphetidine in solution and in the solid state depending on the aryl substituent at the nitrogen atom is discussed.     

Synthesis and photophysical properties of 2,5,8,11‐tetrakis(5‐hexylthiophen‐2‐yl)tetrathieno[2,3‐a:3′,2′‐c:2′′,3′′‐f:3′′′,2′′′‐h]naphthalene

The title compound, C₅₈H₆₄S₈, has been prepared by Pd‐catalysed direct C—H arylation of tetrathienonaphthalene (TTN) with 5‐hexyl‐2‐iodothiophene and recrystallized by slow evaporation from dichloromethane. The crystal structure shows a completely planar geometry of the TTN core, crystallizing in the monoclinic space group P2₁/c. The structure consists of slipped π‐stacks and the interfacial distance between the mean planes of the TTN cores is 3.456 (5) Å, which is slightly larger than that of the comparable derivative of tetrathienoanthracene (TTA) with 2‐hexylthiophene groups. The packing in the two structures is greatly influenced by both the aromatic core of the structure and the alkyl side chains.