6‐Chloroisocytosine and 5‐bromo‐6‐methylisocytosine: again,one or two tautomers present in the same crystal?

It is well known that pyrimidin‐4‐one derivatives are able to adopt either the 1H‐ or the 3H‐tautomeric form in (co)crystals, depending on the coformer. As part of ongoing research to investigate the preferred hydrogen‐bonding patterns of active pharmaceutical ingredients and their model systems, 2‐amino‐6‐chloropyrimidin‐4‐one and 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4‐one have been cocrystallized with several coformers and with each other. Since Cl and Br atoms both have versatile possibilities to interact with the coformers, such as via hydrogen or halogen bonds, their behaviour within the crystal packing was also of interest. The experiments yielded five crystal structures, namely 2‐aminopyridin‐1‐ium 2‐amino‐6‐chloro‐4‐oxo‐4H‐pyrimidin‐3‐ide–2‐amino‐6‐chloropyrimidin‐4(3H)‐one (1/3), C₅H₇N₂⁺·C₄H₃ClN₃O⁻·3C₄H₄ClN₃O, (Ia), 2‐aminopyridin‐1‐ium 2‐amino‐6‐chloro‐4‐oxo‐4H‐pyrimidin‐3‐ide–2‐amino‐6‐chloropyrimidin‐4(3H)‐one–2‐aminopyridine (2/10/1), 2C₅H₇N₂⁺·2C₄H₃ClN₃O⁻·10C₄H₄ClN₃O·C₅H₆N₂, (Ib), the solvent‐free cocrystal 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(1H)‐one (1/1), C₅H₆BrN₃O·C₅H₆BrN₃O, (II), the solvate 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(1H)‐one–N‐methylpyrrolidin‐2‐one (1/1/1), C₅H₆BrN₃O·C₅H₆BrN₃O·C₅H₉NO, (III), and the partial cocrystal 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(1H)‐one–2‐amino‐6‐chloropyrimidin‐4(3H)‐one (0.635/1/0.365), C₅H₆BrN₃O·C₅H₆BrN₃O·C₄H₄ClN₃O, (IV). All five structures show R₂²(8) hydrogen‐bond‐based patterns, either by synthon 2 or by synthon 3, which are related to the Watson–Crick base pairs.     

Evaluation of 1‐arylpiperazine derivative of hydroxybenzamides as 5‐HT1A and 5‐HT7 serotonin receptor ligands: An experimental and molecular modeling approach

The synthesis and evaluation as 5‐HT_1A and 5‐HT₇ serotonin receptor ligands of the two sets of O‐substituted hydroxybenzamides, structurally related to 2‐{3‐[4‐(2‐methoxyphenyl)piperazin‐1‐yl]propoxy}benzamide ( 1 ), (K_i 5‐HT_1A = 21 nM, 5‐HT₇ = 234 nM) are reported. To affect the affinity for 5‐HT_1A and 5‐HT₇ receptors, an amide moiety ( 2 , 3 , 4 , 5 , 6 ) and a hydrocarbon chain length ( 7 , 8 , 9 , 10 ) were modified. The serotonergic activity of compounds 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 was generally higher in the case of 5‐HT_1A receptors compared with 5‐HT₇ ones; the most active 5‐HT_1A ligands being meta‐isomer 2 (K_i = 7 nM) and both analogs of 1 with the longest spacer, i.e., penta‐ and hexa‐methylene derivatives 9 and 10 (K_i = 4 and 3 nM, respectively). The observed biological properties of compounds 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 were elucidated using molecular modeling procedures. J. Heterocyclic Chem., (2010).     

Syntheses,Structures, and Luminescent Properties of d10 Coordination Polymers with 2‐(4‐Carboxyphenyl)‐imidazo[4, 5‐f]‐1, 10‐phenanthroline and 1, 3‐Benzenedicarboxylate Derivatives

Four Zn^II/Cd^II coordination polymers (CPs) based on 2‐(4‐carboxy‐phenyl)imidazo[4, 5‐f]‐1, 10‐phenanthroline (HNCP) and different derivatives of 5‐R‐1, 3‐benzenedicarboxylate (5‐R‐1, 3‐BDC) (R = NO₂, H, OH), [Zn(HNCP)(5‐NO₂‐1, 3‐BDC)]_n ( 1 ), [Cd(HNCP)(5‐NO₂‐1, 3‐BDC)]_n ( 2 ), [Zn(HNCP)(1, 3‐BDC)(H₂O)₂]_n ( 3 ), and {[Zn(HNCP)(5‐OH‐1, 3‐BDC)(H₂O) · H₂O}_n ( 4 ) were synthesized under hydrothermal conditions. Compounds 1 – 4 were determined by elemental analyses, IR spectroscopy, and single‐crystal and powder X‐ray diffraction. Compounds 1 and 2 are isomorphous, presenting a 4‐connected uninodal (4, 4)‐sql 2D framework with threefold interpenetration, which are further extended into the three‐dimensional (3D) supramolecular architecture through π ··· π stacking interactions between the aryl rings of 5‐NO₂‐1, 3‐BDC. Compared to compound 1 , 3 is obtained by using different reaction temperatures and metal‐ligand ratios, generating a 3D framework with –ABAB– fashion via π ··· π stacking interactions. Compound 4 is a 1D chain, which is further extended into a 3D supramolecular net by hydrogen bonds and π ··· π stacking interactions. The thermogravimetric and fluorescence properties of 1 – 4 were also explored.     

Design and synthesis of novel rofecoxib analogs as potential cyclooxygenase (COX‐2) inhibitors: Replacement of the methylsulfonyl pharmacophore by a sulfonylazide bioisostere

A group of rofecoxib analogs, having a sulfonylazide (SO₂N₃) substituent in place of the methanesulfonyl (SO₂CH₃) pharmacophore at the meta‐position viz 3‐(4‐methyl, 4‐methoxy, or 4‐ethoxyphenyl)‐4‐(3‐sulfonylazidophenyl)‐2(5H)furanone ( 7a‐c ) and para‐position viz 3‐phenyl‐4‐(4‐sulfonylazidophenyl)‐2(5H)furanone ( 7d ), 3‐(4‐fluoro, or 4‐chlorophenyl)‐4‐(4‐sulfonylazidophenyl)‐2(5H)furanone ( 7e‐f ) of the C–4 phenyl ring, and 4‐(1‐oxido‐4‐pyridyl)‐3‐phenyl‐2(5H)furanone ( 12 ) were designed and synthesized for evaluation as selective cyclooxygenase‐2 (COX‐2) inhibitors. In vitro COX‐1/COX‐2 enzyme inhibition studies showed that 3‐phenyl‐4‐(4‐sulfonylazidophenyl)‐2(5H)furanone ( 7d ) inhibited COX‐1 selectively (COX‐1 IC₅₀ = 0.6659 μM; COX‐2 IC₅₀ > 100 μM) and 3‐(4‐fluorophenyl)‐4‐(4‐sulfonylazidophenyl)‐2(5H)furanone ( 7e ) inhibited both enzymes (COX‐1 IC₅₀ = 0.8494 μM; COX‐2 IC₅₀ = 1.7661 μM). A molecular modeling study was performed where 3‐(4‐fluorophenyl)‐4‐(4‐sulfonylazidophenyl)‐2(5H)furanone ( 7e ) was docked in the active site of murine COX‐2 isozyme, which showed that the sulfonylazido group inserts deep into the 2°‐pocket of COX‐2 where it undergoes both H‐bonding (Gln¹⁹², Phe⁵¹⁸) and weak electrostatic (Arg⁵¹³) interactions.     

Singlet-Oxygen Ene Reactions of (E)-4-Propyl[1,1,-2H3]oct-4-ene. Short Communication

Rose bengal-sensitized photooxygenation of 4-propyl-4-octene ( 1 ) in MeOH/Me₂CHOH 1:1 (v/v) and MeOH/H₂O 95:5 followed by reduction gave (E)-4-propyl-5-octen-4-ol ( 4 ), its (Z)-isomer 5 , (E)-5-propyl-5-octen-4-ol ( 6 ), and its (Z)-isomer 7 . Analogously, (E)-4-propyl[1,1,1-²H₃]oct-4-ene ( 2 ) gave (E)-4-propyl[1,1,1-²H₃]oct-5-en-4-ol ( 14 ), its (Z)-isomer 15 , (E)-5-[3′,3′,3′-²H₃]propyl-5-octen-4-ol ( 16 ), its (Z)-isomer 17 , and the corresponding [8,8,8-²H₃]-isomers 18 and 19 (see Scheme 1). The proportions of 4–7 were carefully determined by GC between 10% and 85% conversion of 1 and were constant within this range. The labeled substrate 2 was photooxygenated in two high-conversion experiments, and after reduction, the ratios 16/18 and 17/19 were determined by NMR. Isotope effects in 2 were neglected and the proportions of corresponding products from 1 and 2 assumed to be similar (% 4 ≈? % 14 ; % 5 ≈? % 15 ; % 6 ≈? % ( 16 + 18 ): % 7 ≈? % ( 17 + 19 )). Combination of these proportions with the ratios 16/18 and 17/19 led to an estimate of the proportions of hydroperoxides formed from 2 . Accordingly, singlet oxygen ene additions at the disubstituted side of 2 are preferred (ca. 90%). The previously studied trisubstituted olefins 20–25 exhibited the same preference, but had both CH₃ and higher alkyl substituents on the double bond. In these substrates, CH₃ groups syn to the lone alkyl or CH₃ group appear to be more reactive than CH₂ groups at that site beyond a statistical bias.     

Strukturelle Abwandlungen am Vitamin D3. 3. Mitteilung [1]. Synthese und eigenschaften von SO2-addukten des (5Z)- und (5E)-vitamins D3

Structural Modifications of Vitamin D₃. Synthesis and Properties of the SO₂-Adducts with (5 Z )- and (5 E )-Vitamin D₃ Treatment of (5Z)- and (5E)-vitamin D₃ ( 4 ) with sulfur dioxide yields each quantitatively the cyclic sulfones 1a and 1b . Thermally induced elimination of sulfur dioxide leads to either isotachysterol₃ ( 3 ) alone or mixtures of isotachysterol₃ ( 3 ) and isovitamin D₃ ( 2 ). On the other hand the extrusion of SO₂ can be brought about by means of KOH/CH₃OH or on an alumina surface affording (5E)-vitamin D₃ ( 4 ). On treatment with CD₃UD/tBuOK/D₂O 1a and 1b are transformed (5E)-6, 19, 19′-trideuteriovitamin D₃ ( 4a ).     

Flux synthesis of (3,4)-connected zinc phosphites with different framework topologies

Two three-dimensional open-framework zinc phosphites, H₂aem·Zn₃(HPO₃)₄·0.5H₂O (1) and H₂apm·Zn₃(HPO₃)₄ (2), have been synthesized by a phosphorous acid flux method, where aem=4-(2-aminoethyl)morpholine and apm=4-(3-aminopropyl)morpholine. Compound 1 crystallizes in the monoclinic system, P2₁/c, a=9.5852(7) Å, b=20.3941(8) Å, c=10.5339(8) Å, β=94.125(9)°, V=2053.8(2) Å³, Z=4, R₁=0.0319, wR₂=0.0628. Compound 2 crystallizes in the monoclinic system, P2₁/n, a=8.589(2) Å, b=14.020(3) Å, c=16.606(3) Å, β=97.190(8)°, V=1983.9(7) Å³, Z=4, R₁=0.0692, wR₂=0.1479. Both compounds are based on (3,4)-connected networks with 8- and 12-ring channels, which are constructed from Zn₃(HPO₃)₄ clusters as the same secondary building units. These inorganic clusters are spatially organized by different structure-directing agents into different three-dimensional frameworks.     

Synthesis of two metabolites of 2,4-diamino-5(3,4,5-trimethoxybenzyl)-pyrimidines (Trimethoprim)

The synthesis of two metabolites M₃ and M₄ of 2,4-diamino-5-(3, 4, 5-trimethoxybenzyl)-pyrimidine (trimethoprim, 1 ) is reported. M₃ (trimethoprim 1-oxide) as well as the isomeric 3-oxide were prepared by oxidation of 1 with m-chloroperbenzoic acid. The structure of M₃ was finally established by x-ra analysis [4]. The metabolite M₄ [2, 4-diamino-5-(3-hydroxy-4, 5-dimethoxy-benzyl)-pyrimidine] was prepared by condensation of 3-benzyloxy-4, 5-dimethoxybenzaldehyde ( 2 ) with 3-methoxypropionitrile ( 3 ) and guanidine followed by hydrogenolysis of the intermediate 3-benzyloxy compound 4 .     

Complexes containing the unit Rh2 P PM (M = Cr or Mn, P P = bis(diphenylphosphino) alkane); the independence of the metal centres

Treatment of (η⁵-C₅H₅)₂Rh₂(CO)η¹-Ph₂P(CH₂)_n PPh₂(μ-η¹:η¹-CF₃C₂CF₃) (I) with (η⁵-CH₃C₅H₄)Mn(CO)₂(thf) or Cr(CO)₅(thf) gives the hetero-trinuclear products (η-C₅H₅)₂Rh₂(CO)(μ-CF₃C₂CF₃)μ:η¹:η¹-Ph₂P(CH₂)_nPPh₂(η-CH₃C₅H₃C₄)Mn(CO₂) (II, n = 1–4) and (η⁵-C₅H₅)₂Rh₂(CO)(μ-CF₃C₂CF₃)μ:η¹:η¹-Ph₂P(CH₂)nPPh₂Cr(CO)₅ (IV, n = 1–4) in good yields. In these products, the configuration of the CO and bisphosphine units on the Rh-Rh bond is trans. Related reactions between (η⁵:η⁵-C₅H₄CH₂C₅H₄)Rh₂(CO)η¹-Ph₂P(CH₂)nPPh₂(μ-η¹:η¹- (V) and the same solvated manganese and chromium complexes give (η⁵:η⁵-C₅H₄CH₂C₅H₄)Rh₂(CO)(μ-CF₃C₂CF₃)μ:η¹:η¹-Ph₂P(CH₂) (VI, n = 1, 2 or 4) and (η⁵:η⁵-C₅H₄CH₂C₅H₄)Rh₂(CO)(μ-CF₃C₂CF₃)μ:η¹:η¹-Ph₂P(CH₂) (VIII). The complexes (VI) and (VIII) have a mutually cis arrangement of CO and the bisphosphine on the Rh-Rh bond. Attempts to induce the complexes (IV), (V), (VI), and (VIII) to form clusters by loss of CO and Rh-M bond formation were not successful. Treatment with trimethylamine oxide or sunlight irradiation generally resulted in loss of the hetero-metal and formation of the dirhodium phosphine oxide complexes (III, n = 2 or 4) and (VII, n = 2, 3).     

Syntheses,Crystal Structures and Thermal Behavior of Five New Complexes Containing 2, 4, 6‐Trifluorobenzoate as Ligand

Five new complexes containing 2, 4, 6‐trifluorobenzoateas ligand have been synthesized and structurally characterized, namely Li(C₆F₃H₂COO)(H₂O) (P2₁, Z = 2, 1 ),Cs(C₆F₃H₂COO)(C₆F₃H₂COOH) (P2₁/c, Z = 4, 2 ),Cu(C₆F₃H₂COO)₂(H₂O)₂ (P$\bar{1}$ , Z = 1, 3 ), Cu(C₆F₃H₂COO)₂(MeOH) (P2₁/c. Z = 4, 4 ) and Ag(C₆F₃H₂COO)(H₂O) (C2/c, Z = 8, 5 ). 1 – 3 and 5 are coordination polymers forming strands ( 1 , 3 , 5 ) or corrugated layers ( 2 ). In 1 and 2 the benzoate ligand acts as a bridging ligand, whereas in 3 and 5 the benzoate ligand is not bridging and the molecular units are interconnected by bridging water molecules. In 4 and 5, dimeric Cu₂ and Ag₂ units, respectively, are formed with short M ··· M contacts. The dimeric units in 4 resemble the well‐known paddlewheel structural motif. In 5 these dimeric units are further connected by bridging water molecules, whereas in 4 only very weak F ··· H interactions connect the dimeric units. DTA/TG experiments on 1 , 3 and 4 reveal that in a first step solvent molecules (H₂O, MeOH) are unquestionably released. In 1 – 5 the torsion angles of the carboxylate group with respect to the aromatic ring deviate significantly from zero. These results are in very good agreement with the results of quantum chemical calculations of free 2, 4, 6‐trifluorobenzoic acid and its dimer at the DFT and RI‐MP2 level of theory.     

Breaking the Mirror: pH‐Controlled Chirality Generation from a meso Ligand to a Racemic Ligand

To study the conversion from a meso form to a racemic form of tetrahydrofurantetracarboxylic acid (H₄L), seven novel coordination polymers were synthesized by the hydrothermal reaction of Zn(NO₃)₂ ? 6 H₂O with (2S,3S,4R,5R)‐H₄L in the presence of 1,10‐phenanthroline (phen), 2,2′‐bipyridine (2,2′‐bpy), or 4,4′‐bipyridine (4,4′‐bpy): [Zn₂{(2S,3S,4R,5R)‐L}(phen)₂(H₂O)] ? 2 H₂O ( 1 ), [Zn₄{(2S,3R,4R,5R)‐L}{(2S,3S,4S,5R)‐L}(phen)₂(H₂O)₂] ( 2 ), [Zn₂{(2S,3S,4R,5R)‐L}(H₂O)₂] ? H₂O ( 3 ), [Zn₄{(2S,3R,4R,5R)‐L}{(2S,3S,4S,5R)‐L} (2,2′‐bpy)₂(H₂O)₂] ? 2 H₂O ( 4 ), [Zn₂ {(2S,3S,4R,5R)‐L}(2,2′‐bpy)(H₂O)] ( 5 ), [Zn₄{(2S,3R,4R,5R)‐L}{(2S,3S,4S,5R)‐L} (4,4′‐bpy)₂(H₂O)₂] ( 6 ), and [Zn₂ {(2S,3S,4R,5R)‐L}(4,4′‐bpy)(H₂O)] ? 2 H₂O ( 7 ). These complexes were obtained by control of the pH values of reaction mixtures, with an initial of pH 2.0 for 1 , 2.5 for 2 , 4 , and 6 , and 4.5 for 3 , 5 , and 7 , respectively. The expected configuration conversion has been successfully realized during the formation of 2 , 4 , and 6 , and the enantiomers of L, (2S,3R,4R,5R)‐L and (2S,3S,4S,5R)‐L, are trapped in them, whereas L ligands in the other four complexes retain the original meso form, which indicates that such a conversion is possibly pH controlled. Acid‐catalyzed enol–keto tautomerism has been introduced to explain the mechanism of this conversion. Complex 1 features a simple 1D metal–L chain that is extended into a 3D supramolecular structure by π–π packing interactions between phen ligands and hydrogen bonds. Complex 2 has 2D racemic layers that consist of centrosymmetric bimetallic units, and a final 3D supramolecular framework is formed by the interlinking of these layers through π–π packing interactions of phen. Complex 3 is a 3D metal–organic framework (MOF) involving meso‐L ligands, which can be regarded as (4,6)‐connected nets with vertex symbol (4⁵.6)(4⁷.6⁸). Complexes 4 and 5 contain 2D racemic layers and (6,3)‐honeycomb layers, respectively, both of which are combined into 3D supramolecular structures through π–π packing interactions of 2,2′‐bpy. The structure of complex 6 is a 2D network formed by 4,4′‐bpy bridging 1D tubes, which consist of metal atoms and enantiomers of L. These layers are connected through hydrogen bonds to give the final 3D porous supramolecular framework of 6 . Complex 7 is a 3D MOF with novel (3,4,5)‐connected (6³)(4².6⁴)(4².6⁶.8²) topology. The thermal stability of these compounds was also investigated.     

Syntheses and Characterization of Molybdenum Complexes with the (1,3-Dithioliumyl)diphenylphosphine Containing Ligands

Treatment of [Et₄N][Mo(CO)₅(PPh₂CS₂)], 1 with unsaturated organic halides afforded the neutral complexes Mo(CO)₅(PPh₂CS₂R) (R = CH₂CN, 2 ; R = CH₂C≡CH, 3 ). Alkylation reactions take place at the sulfur atom. Protonation of complex 2 and 3 with HBF₄ produced the intramolecular cyclization products [Mo(CO)₅(PPh₂CS₂C₂H₃N)][BF₄], 4 and [Mo(CO)₅(PPh₂CS₂C₃H₄)][BF₄], 5 , respectively. In complex 4 and 5 , two five-membered 1,3-dithiolium rings formed. Protonation of 3 to 5 is not reversible, but deprotonation of 4 by n-BuLi or PPh₃ gave 2 quantitatively. Treatment of 4 with n-Bu₄NF yielded complex Mo(CO)₅PPh₂F, 6 and 2 with 1:1 ratio, but in the reaction of 5 and n-Bu₄NF only compound 6 was formed. All of these complexes are identified by spectroscopic methods.     

Ringsubstituierte [1]titanocenophane

The ring-substituted bis(cyclopentadienyl)silanesMe ₂Si(C₅H₅) (MeC₅H₄) (1a) andMe ₂Si(MeC₅H₄)₂ (2a) could be prepared by the reactions ofMe ₂SiCl₂ with C₅H₅Na andMeC₅H₄Na or only withMeC₅H₄Na, respectively. Metallation of1 a or2 a withn-BuLi and following reaction with TiCl₄ led to the first ringsubstituted [1]titanocenophanes,Me ₂Si(C₅H₄) (MeC₅H₃)TiCl₂ (1 b) orMe ₂Si(MeC₅H₃)₂ TiCl₂ (2 b), respectively. On reaction with NaI,1 b yieldedMe ₂Si(C₅H₄) (MeC₅H₃)TiI₂ (1 c). Structural assignments of the compounds could be made on the basis of their¹H NMR spectra.

     

Eight new crystal structures of 5‐(hydroxymethyl)uracil, 5‐carboxyuracil and 5‐carboxy‐2‐thiouracil: insights into the hydrogen‐bonded networks and the predominant conformations of the C5‐bound residues

In order to examine the preferred hydrogen‐bonding pattern of various uracil derivatives, namely 5‐(hydroxymethyl)uracil, 5‐carboxyuracil and 5‐carboxy‐2‐thiouracil, and for a conformational study, crystallization experiments yielded eight different structures: 5‐(hydroxymethyl)uracil, C₅H₆N₂O₃, (I), 5‐carboxyuracil–N,N‐dimethylformamide (1/1), C₅H₄N₂O₄·C₃H₇NO, (II), 5‐carboxyuracil–dimethyl sulfoxide (1/1), C₅H₄N₂O₄·C₂H₆OS, (III), 5‐carboxyuracil–N,N‐dimethylacetamide (1/1), C₅H₄N₂O₄·C₄H₉NO, (IV), 5‐carboxy‐2‐thiouracil–N,N‐dimethylformamide (1/1), C₅H₄N₂O₃S·C₃H₇NO, (V), 5‐carboxy‐2‐thiouracil–dimethyl sulfoxide (1/1), C₅H₄N₂O₃S·C₂H₆OS, (VI), 5‐carboxy‐2‐thiouracil–1,4‐dioxane (2/3), 2C₅H₄N₂O₃S·3C₆H₁₂O₃, (VII), and 5‐carboxy‐2‐thiouracil, C₁₀H₈N₄O₆S₂, (VIII). While the six solvated structures, i.e. (II)–(VII), contain intramolecular S(6) O—H…O hydrogen‐bond motifs between the carboxy and carbonyl groups, the usually favoured R₂²(8) pattern between two carboxy groups is formed in the solvent‐free structure, i.e. (VIII). Further R₂²(8) hydrogen‐bond motifs involving either two N—H…O or two N—H…S hydrogen bonds were observed in three crystal structures, namely (I), (IV) and (VIII). In all eight structures, the residue at the ring 5‐position shows a coplanar arrangement with respect to the pyrimidine ring which is in agreement with a search of the Cambridge Structural Database for six‐membered cyclic compounds containing a carboxy group. The search confirmed that coplanarity between the carboxy group and the cyclic residue is strongly favoured.     

Synthesis of <Emphasis Type="Italic">N</Emphasis>-containing drimane sesquiterpenoids from 11-dihomodriman-8α-ol-12-one

Beckmann reaction products of 11-dihomodriman-8α-ol-12-one oxime with Ac₂O in pyridine, 86% H₃PO₄, p-TsCl in pyridine, and PCl₅ in ether were investigated. It has been found that the major product from treatment of the oxime with Ac₂O is the oxime acetate. Reaction of the oxime with 86% H₃PO₄ gave (1S,2S,4aS,8aS)-2,5,5,8a-tetramethyldecahydro-1H-naphtho[1, 2][5, 6]-3-methyl-4,5-dihydro[1, 2, 6]oxazine; with p-TsCl, (1S,2S,4aS,8aS)-2,5,5,8a-tetramethyldecahydro-1H-naphtho[1, 2][5, 6]-2-methyl-4,5dihydro[1, 3, 6]oxazine; with PCl₅, a mixture of products containing 11-acetylamino- and 11-methylaminooxodrimenes that were isomeric at the double bond, norambreinolide, and a 1,3,6-oxazine.     

A new double‐cube nitride complex containing titanium and potassium

The reaction of the imide–nitride complex [{Ti(η⁵‐C₅Me₅)(μ‐NH)}₃(μ₃‐N)] with potassium iodide in pyridine at room temperature affords the adduct di‐μ‐iodido‐1:1′κ⁴I‐bis{tri‐μ₃‐imido‐1:2:3κ³N;1:2:4κ³N;1:3:4κ³N‐μ₃‐nitrido‐2:3:4κ³N‐tris[2,3,4(η⁵)‐pentamethylcyclopentadienyl](pyridine‐1κN)‐tetrahedro‐potassiumtrititanium(IV)}, [K₂Ti₆(C₁₀H₁₅)₆I₂N₂(NH)₆(C₅H₅N)₂] or [(C₅H₅N)(μ‐I)K{(μ₃‐NH)₃Ti₃(η⁵‐C₅Me₅)₃(μ₃‐N)}]₂. The crystal structure contains two [KTi₃N₄] cube‐type units held together by two bridging I atoms. There is a centre of inversion located in the middle of this unprecedented discrete K₂I₂ unit. The geometry around K is best described as distorted trigonal prismatic, with three imide groups, two bridging I atoms and one pyridine ligand.     

3-Hydrazino-1,2,4-triazin-5(2H)-ones in Reactions with Compounds Containing Carbonyl and Active Methylene Groups

Boiling of ethyl cyanoacetate with 6-tert-butyl-3-hydrazino-1'2'4-triazin-5(2H)-one in alkalinemedium yielded 6-tert-butyl-3-(5-hydroxy-3-oxo-2'3-dihydro-1H-pyrazol-1-yl)-1'2'4-triazin-5(2H)-one.Acylation of 6-tert-butyl-3-hydrazino-1'2'4-triazin-5(2H)-one with benzoyl chloride furnished 3-benzoyl-hydrazido-1'2'4-triazine that cyclized when treated with POCl₃ providing a derivative of[1'2'4]triazolo[4'3-b][1'2'4]triazine. Boiling of 6-tert-butyl-3-hydrazino-1'2'4-triazin-5(2H)-one in glacialacetic acid gave rise to diacetylated derivative whereas the boiling with acetic anhydride in an inert solventafforded monoacetylated product.     

Transformations of Perfluorinated 2-Alkyl- and 2,2-Dialkylbenzocyclobutenones in SbF<Subscript>5</Subscript> and SiO<Subscript>2</Subscript>-SbF<Subscript>5</Subscript>

Perfluorinated 2-methyl- and 2-ethylbenzocyclobutenones on heating in SbF₅ underwent isomerization into perfluoroindan-1-one and perfluoro(2-methylindan-1-one), while their reaction with SiO₂—SbF₅ gave perfluorinated 3-methyl- and 3-ethylphthalides, respectively. Perfluorinated 2-ethyl-2-methyl- and 2,2-diethylbenzocyclobutenones reacted with SbF₅ to produce perfluorinated 2-(but-2-en-2-yl)- and 2-(pent-2-en-3-yl)-benzoic acids, and their transformations in SbF₅ over SiO₂ afforded 5,6,7,8-tetrafluoro-1-oxo-3-trifluoromethyl-1H-isochromene-4-carboxylic acid and perfluoro(4-ethyl-3-methyl-1H-isochromen-1-one), respectively.     

Architecture of the rings of 5-arylidenerhodanine derivatives versus P-gp inhibition

5-Arylidene derivatives of rhodanine show various biological activities. The new crystal structures of five derivatives investigated towards ABCB1 efflux pump modulation are reported, namely, 2-[5-([1,1′-biphenyl]-4-ylmethylidene]-4-oxo-2-thioxothiazolidin-3-yl)acetic acid dimethyl sulfoxide monosolvate, C₁₈H₁₃NO₃S₂·C₂H₆OS ( 1 ), 4-[5-([1,1′-biphenyl]-4-ylmethylidene]-4-oxo-2-thioxothiazolidin-3-yl)butanoic acid, C₂₀H₁₇NO₃S₂ ( 2 ), 5-[4-(benzyloxy)benzylidene]-2-thioxothiazolidin-4-one, C₁₇H₁₃NO₂S₂ ( 3 ), 4-{5-[4-(benzyloxy)benzylidene]-4-oxo-2-thioxothiazolidin-3-yl}butanoic acid, C₂₁H₁₉NO₄S₂ ( 4 ), and 5-[4-(diphenylamino)benzylidene]-2-thioxothiazolidin-4-one, C₂₂H₁₆N₂OS₂ ( 5 ). Compounds 1 and 3 – 5 crystallize in the triclinic space group P, while 2 crystallizes in the monoclinic space group P2₁/n, where the biphenyl moiety is observed in two positions (A and B). Two molecules are present in the asymmetric unit of 5 and, for the other four compounds, there is only one molecule; moreover, 1 crystallizes with one dimethyl sulfoxide molecule. The packing of the molecules containing a carboxyl group ( 1 , 2 and 4 ) is determined by O—H…O hydrogen bonds, while in the other two compounds ( 3 and 5 ), the packing is determined by N—H…O hydrogen bonds. Additionally, induced-fit docking studies have been performed for the active compounds to investigate their putative binding mode inside the human glycoprotein P (P-gp) binding pocket.