The Structures of Indazolin‐3‐one (=1,2‐Dihydro‐3H‐indazol‐3‐one) and 7‐Nitroindazolin‐3‐one

The existence of polymorphism in parent indazolin‐3‐one (=1,2‐dihydro‐3H‐indazol‐3‐one; 1 ) is reported as well as an X‐ray and NMR CPMAS study establishing that its 7‐nitro derivative 2 exists as the 3‐hydroxy tautomer. Absolute shieldings calculated at the GIAO/B3LYP/6‐311++G(d,p) level were used to determine the tautomeric oxo/hydroxy equilibrium in solution, i.e., always the 1H‐indazol‐3‐ol tautomer predominates.     

A New Germanium Complex Containing Chelating Pyridinecarboxylate Ligands: cis‐Dihydroxybis(pyridine‐2‐carboxylato‐κN1,κO2)germanium Hydrate (1 : 2) (cis‐[Ge(pyca)2(OH)2]⋅2 H2O)

A new germanium complex, cis‐[Ge(pyca)₂(OH)₂]?2 H₂O ( 1 ; pyca=pyridine‐2‐carboxylato), was synthesized by the reaction of [Ge(acac)₂Cl₂] (acac=acetylacetonato=pentane‐2,4‐dionato) with potassium pyridine‐2‐carboxylate (Kpyca) in H₂O/THF. According to the single‐crystal X‐ray diffraction analysis, each Ge‐atom of 1 is coordinated by two pyca ligands and two OH^? groups (Fig. 1). These molecules are bonded to each other via a system of H‐bonds resulting in a sheet‐like structure (Fig. 2). The complex is decomposed during heating with stepwise mass loss and formation of GeO₂ as final product (Fig. 3).     

Diastereoselective Alkyl Grignard 1,4‐Additions to para‐Substituted (2R)‐N‐Cinnamoylbornane‐10,2‐sultam Derivatives: Influence of N‐Atom Pyramidalization

Several typical ¹³C‐NMR displacements (of C?O, C(α), C(β), and C_ipso), as well as conformational or energy properties (S? N? C?O dihedral angle, ΔE syn/anti; HOMO/LUMO) could be correlated with the electronic parameters of p‐substituted N‐cinnamoylbornane‐10,2‐sultams 2 . Even under nonchelating conditions, the pyramidalization of the sultam N‐atom decreases for electron‐attracting p‐substituents, inducing a modification of the sultam‐ring puckering. Detailed comparison of the X‐ray structure analyses of 2b, 2d , and 2m showed that the orientation of the sterically directing pseudo‐axial S?O(2) and H? C(2) is modified and precludes any conclusion about the π‐facial stereoelectronic influence of the N lone pair on the alkyl Grignard 1,4‐addition. We also showed that the aggregating alkyl Grignard reagent may be used in equimolar fashion, demonstrating that the sultam moiety is chelated with a Lewis acid such as MgBr₂. The Schlenk equilibrium may also be used to generate the appropriate conditions of effective 1,4‐diastereoselectivity. Although the anti‐s‐cis/syn‐s‐cis difference of conformational energies for N‐cinnamoyl derivatives 2 is higher than for the simple N‐crotonoyl analogue, an X‐ray structure analysis of the SO₂/C?O syn derivative 10 confirms the predictive validity of our conformational calculations for ΔE≤1.8 kcal/mol.     

(4,4′‐Bipyridine)mercury(II) Coordination Polymers,Syntheses, and Structures

Mercury(II) complexes with 4,4′‐bipyridine (4,4′‐bipy) ligand were synthesized and characterized by elemental analysis, and IR, ¹H‐ and ¹³C‐NMR spectroscopy. The structures of the complexes [Hg₃(4,4′‐bipy)₂(CH₃COO)₂(SCN)₄]_n ( 1 ), [Hg₅(4,4′‐bipy)₅(SCN)₁₀]_n ( 2 ), [Hg₂(4,4′‐bipy)₂(CH₃COO)₂]_n(ClO₄)_2n ( 3 ), and [Hg(4,4′‐bipy)I₂]_n ( 4 ) were determined by X‐ray crystallography. The single‐crystal X‐ray data show that 2 and 4 are one‐dimensional zigzag polymers with four‐coordinate Hg‐atoms, whereas 1 is a one‐dimensional helical chain with two four‐coordinate and one six‐coordinate Hg‐atom. Complex 3 is a two‐dimensional polymer with a five‐coordinate Hg‐atom. These results show the capacity of the Hg‐ion to act as a soft acid that is capable to form compounds with coordination numbers four, five, and six and consequently to produce different forms of coordination polymers, containing one‐ and two‐dimensional networks.     

X‐Ray Structure Study of an Unusual 13,14,15,16‐Tetranorlabdane Derivative Obtained in the Synthesis of (7α)‐7,8‐Dihydroxy‐14,15‐dinorlabdane‐11,13‐dione

The unconventional (5S,7R,8S,9R,10S)‐configurated (?)‐7‐(acetyloxy)‐12,12‐dichloro‐8‐hydroxy‐13,14,15,16‐tetranorlabdan‐11‐one ( 2 ) was synthesized via the HCl‐promoted hydrolysis of (7α)‐7,8‐(isopropylidenedioxy)‐14,15‐dinorlabdan‐11,13‐dione ( 5 ). Possible mechanistic pathways of the reaction are considered. Crystal and molecular structures of the isolated compound 2 were determined by single‐crystal X‐ray structure analysis.     

Methyl Pothoscandensate,a New ent‐18(4→3)‐Abeokaurane from Pothos scandens

Methyl pothoscandensate ( 1 ), a new molecular skeleton of ent‐18(4→3)‐abeokaurane, along with eight known compounds was isolated from the whole plant of Pothos scandens. The structure of the new compound was established by spectroscopic techniques and confirmed by single‐crystal X‐ray diffraction. The inhibitory activity of selected compounds against porcine respiratory and reproductive syndrome virus (PRRSV) was measured by the cytopathic effect (CPE) method. Compound 1 showed weak effect on PRRSV with an IC₅₀ value of 40.3±8.3 μM (TI=15.7).     

Synthesis and Structure of O,O‐Diethyl N‐[(trans‐4‐Aryl‐5,5‐dimethyl‐2‐oxido‐2λ5‐1,3,2‐dioxaphosphorinan‐2‐yl)methyl]phosphoramidothioates

A study on the synthesis of the novel N‐(cyclic phosphonate)‐substituted phosphoramidothioates, i.e., O,O‐diethyl N‐[(trans‐4‐aryl‐5,5‐dimethyl‐2‐oxido‐2λ⁵‐1,3,2‐dioxaphosphorinan‐2‐yl)methyl]phosphoramidothioates 4a – l , from O,O‐diethyl phosphoramidothioate ( 1 ), a benzaldehyde or ketone 2 , and a 1,3,2‐dioxaphosphorinane 2‐oxide 3 was carried out (Scheme 1 and Table 1). Some of their stereoisomers were isolated, and their structure was established. The presence of acetyl chloride was essential for this reaction and accelerated the process of intramolecular dehydration of intermediate 5 forming the corresponding Schiff base 7 (Scheme 2).     

2‐Amino‐1,2,3,6‐tetrahydro‐6‐oxocyclopenta[c]fluorene‐2‐carboxylic Acid (FlAib), a Completely Rigidified,Fluoren‐9‐one‐Based α‐Amino Acid

The synthesis, optical resolution, determination of absolute configuration and conformational preference, and spectroscopic characteristics of terminally protected (blocked) derivatives and short peptides of 2‐amino‐1,2,3,6‐tetrahydro‐6‐oxocyclopenta[c]fluorene‐2‐carboxylic acid (FlAib), a novel, rigid, chiral, cyclized C^α,α‐disubstituted glycine are described.     

The Structure of 2‐[(1S)‐(+)‐10‐camphorsulfonamino]‐6‐aminopyridine in the Solid State and in Solution; Unprecedented Cocrystallization of Four Stereoisomers

The solid and solution structures of a new optically active aminopyridine compound, 2‐[(1S)‐(+)‐10‐camphorsulfonamino]‐6‐aminopyridine [(S)‐csaap], 1 , are reported. Crystal data: space group P2₁, a = 8.9729 (5), b = 10.9447 (6), c = 36.693 (2) Å, β = 96.435 (1)°, V = 3580.8 (3) ų, Z = 8, R₁ = 0.0673 and wR₂ = 0.1600 with I > 2σ(I). This chiral compound shows an unprecedented cocrystallization of four stereoisomers, which are characterized by X‐ray crystallography and NMR spectroscopy.     

Regioselective [3+3] Cyclization of 1,3‐Bis(silyloxy)buta‐1,3‐dienes with 1,1,1‐Trifluoro‐4‐(silyloxy)alk‐3‐en‐2‐ones: New and Convenient Synthesis of Functionalized 5‐Alkyl‐3‐(trifluoromethyl)phenols

Functionalized 5‐alkyl‐3‐(trifluoromethyl)phenols were prepared by formal [3+3] cyclization of 1,3‐bis(silyloxy)buta‐1,3‐dienes with 1,1,1‐trifluoro‐4‐(silyloxy)alk‐3‐en‐2‐ones derived from 1,1,1‐trifluoroalkane‐2,4‐diones. The latter were prepared by condensation of the dianion of 1,1,1‐trifluoropentane‐2,4‐dione with alkyl halides.     

Exaltone® (=Cyclopentadecanone) from Isomuscone® (=Cyclohexadecanone), a One‐C‐Atom Ring‐Contraction Methodology via a Stereospecific Favorskii Rearrangement: Regioselective Application to (−)‐(R)‐Muscone

Treatment of cyclohexadecanone ( 1g ; with I₂ (2.2 mol‐euqiv.) and KOH in MeOH) furnished the unsaturated (Z)‐ester 2g in 83% yield, via a stereospecific Favorskii rearrangement (Scheme 1). Further treatment with 3‐chloroperbenzoic acid (m‐CPBA) afforded the unreported epoxy ester 3g (88% yield), which was cleaved in 33% yield to Exaltone^® (=cyclopentadecanone; 1f ) with NaOH in MeOH/H₂O and then HCl at 65°. This methodology was similarly extended to higher (C₁₇) and lower (C₁₅ to C₁₁) cyclic ketone analogues, as well as regioselectively to (?)‐(R)‐muscone ( 5c ) and homomuscone ( 5f ) (Scheme 2). Olfactive properties of the corresponding macrocyclic 1‐oxaspiro[2,n]alkanes and ‐alkenes 4 and 8 , resulting from a Corey? Chaykovsky oxiranylation, are also presented.     

Synthesis and Anti‐HIV Activity of Triazolo‐Fused 3′,5′‐Cyclic Nucleoside Analogues Derived from an Intramolecular Huisgen 1,3‐Dipolar Cycloaddition

Triazolo‐fused 3′,5′‐cyclic nucleoside analogues were synthesized by an intramolecular 1,3‐dipolar cycloaddition of nucleoside‐derived azido‐alkynes in a regio‐ and stereospecific manner. The thymine nucleoside base in these target compounds was transformed successfully into the corresponding 5‐methylcytosine component. The synthesized compounds were examined in a MAGI assay for exploring the anti‐HIV activity and in a H9 T lymphocytes assay for measuring the cell toxicity.     

Selenium‐Containing Heterocycles from Isoselenocyanates: Synthesis of 5‐Amino‐2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐selones

The reaction of S‐methylisothiosemicarbazide hydroiodide (=S‐methyl hydrazinecarboximidothioate hydroiodide; 1 ), prepared from thiosemicarbazide by treatment with MeI in EtOH, and aryl isoselenocyanates 5 in CH₂Cl₂ affords 3H‐1,2,4‐triazole‐3‐selone derivatives 7 in good yield (Scheme 2, Table 1). During attempted crystallization, these products undergo an oxidative dimerization to give the corresponding bis(4H‐1,2,4‐triazol‐3‐yl) diselenides 11 (Scheme 3). The structure of 11a was established by X‐ray crystallography.     

A Novel Route to 1‐Substituted 3‐(Dialkylamino)‐9‐oxo‐9H‐indeno[2,1‐c]pyridine‐4‐carbonitriles

Heptalenecarbaldehydes 1 / 1′ as well as aromatic aldehydes react with 3‐(dicyanomethylidene)‐indan‐1‐one in boiling EtOH and in the presence of secondary amines to yield 3‐(dialkylamino)‐1,2‐dihydro‐9‐oxo‐9H‐indeno[2,1‐c]pyridine‐4‐carbonitriles (Schemes 2 and 4, and Fig. 1). The 1,2‐dihydro forms can be dehydrogenated easily with KMnO₄ in acetone at 0° (Scheme 3) or chloranil (=2,3,5,6‐tetrachlorocyclohexa‐2,5‐diene‐1,4‐dione) in a ‘one‐pot’ reaction in dioxane at ambient temperature (Table 1). The structures of the indeno[2,1‐c]pyridine‐4‐carbonitriles 5′ and 6a have been verified by X‐ray crystal‐structure analyses (Fig. 2 and 4). The inherent merocyanine system of the dihydro forms results in a broad absorption band in the range of 515–530 nm in their UV/VIS spectra (Table 2 and Fig. 3). The dehydrogenated compounds 5, 5′ , and 7a – 7f exhibit their longest‐wavelength absorption maximum at ca. 380 nm (Table 2). In contrast to 5 and 5′, 7a – 7f in solution exhibit a blue‐green fluorescence with emission bands at around 460 and 480 nm (Table 4 and Fig. 5).     

Synthesis and Structural Characterization of Cadmium(II) and Mercury(II) Complexes Derived from 3‐Aminoquinoline

Two novel metal complexes derived from interactions of Cd²⁺ and Hg²⁺ ions with 3‐aminoquinoline in the molar ratio 1 : 2 are reported. The synthesized and isolated metal complexes were characterized by UV/VIS, FT‐IR, ¹H‐ and ¹³C‐NMR, and ESI‐MS spectroscopic studies, and elemental analyses. FT‐IR and NMR studies confirmed that the NH₂ group remains uncoordinated in both synthesized complexes. The molecular structure of the Cd^II complex was additionally determined by X‐ray single‐crystal analysis. The Cd complex crystallizes in the triclinic centrosymmetric P$\bar 1$ space group. Moreover, the Cd^II complex exists as neutral discrete molecule and was found to show tetrahedral geometry.     

Synthesis of Derivatives of the Optically Active β‐Amino Acids from (+)‐Car‐2‐ene

The reaction of (+)‐car‐2‐ene ( 4 ) with chlorosulfonyl isocyanate (=sulfuryl chloride isocyanate; ClSO₂NCO) led to the tricyclic lactams 6 and 8 corresponding to the initial formation both of the tertiary carbenium and α‐cyclopropylcarbenium ions (Scheme 2). A number of optically active derivatives of β‐amino acids which are promising compounds for further use in asymmetric synthesis were synthesized from the lactams (see 16, 17 , and 19 – 21 in Scheme 3).     

Synthesis,Characterization, Crystal and Molecular Structure of 1,5‐Dihydro‐2H‐cyclopenta[1,2‐b:5,4‐b′]dipyridin‐2‐imine

The reaction of 1,5‐dihydro‐2H‐cyclopenta[1,2‐b:5,4‐b′]dipyridin‐2‐one ( 3 ) with an alkylamine (butylamine, hexylamine or ethylenediamine) yields, quite unexpectedly and in the absence of catalyst, the novel compound 1,5‐dihydro‐2H‐cyclopenta[1,2‐b:5,4‐b′]dipyridin‐2‐imine ( 4 ) as the sole, analytically pure, solid product, which was fully characterized. The structure of 4 was unequivocally solved by single‐crystal X‐ray‐diffraction analysis. The compound crystallizes in a monoclinic cell (space group P 2₁/c), with two molecules in the asymmetric unit, held together by intermolecular H‐bonds. Compound 4 could be interesting as a bi‐ or even tridentate ligand, and exhibits a strong fluorescence upon excitation at 310 nm. A mechanism, based on the observed C? N bond cleavage, is proposed.     

Selenium‐Containing Heterocycles from Isoselenocyanates: Base‐Catalyzed Reaction of Malononitrile with Phenyl Isoselenocyanate and Bromoacetonitrile or α‐Halogenated Ketones

The reaction of phenyl isoselenocyanate ( 1a ) with malononitrile (=propanedinitrile) in DMF in the presence of Et₃N leads to the intermediate ketene N,Se‐hemiacetal 6a , which can be trapped with bromoacetonitrile or α‐halogenated ketones 12a and 12b (Scheme 3). The products are [(alkylseleno)(phenylamino)methylene]malononitriles 10 and 13 , which are obtained in good yield. In the case of the (2‐oxoalkyl)seleno derivatives 13 , they are in equilibrium with the cyclic hemiacetals 14 . Chemical and spectroscopic evidence for the structures of the new compounds are described. The structure of 14a was established by X‐ray crystallography.     

1,2‐Bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile: (2+2) Cycloadditions with Vinyl Ethers

The title compound (short version: BTE) occurs in (E)‐ and (Z)‐isomers (both with b.p. of ca. 100°) which equilibrate with nucleophilic catalysts. Both undergo (2+2) cycloadditions with methyl vinyl ether at 25°. Three stereogenic centers in the cyclobutanes led to four rac‐diastereoisomers, which were obtained in pure and crystalline state. The structures were elucidated by ¹⁹F‐NMR spectroscopy and confirmed by two X‐ray analyses. The cycloadditions were not stereospecific: e.g., (E)‐BTE furnished 73% trans‐adducts (with respect to the CF₃ groups) and 27% cis‐adducts. The loss of stereochemical integrity occurs in the intermediate gauche‐zwitterions which can cyclize or rotate, but not dissociate. Under extreme conditions (2M LiClO₄ in Et₂O, 70°, 3 months), the thermodynamic equilibrium of the four cyclobutanes was achieved. Considerations of Coulombic attraction and conformational strain in the zwitterionic intermediates allow us to rationalize the observed proportions of diastereoisomeric cyclobutanes. Ethyl vinyl ether and butyl vinyl ether furnished cyclobutanes in similar diastereoisomer ratios.     

Palladium(II) Complexes of the Thiosemicarbazone and N‐Ethylthiosemicarbazone of 3‐Hydroxypyridine‐2‐carbaldehyde: Synthesis,Properties, and X‐Ray Crystal Structure

Two novel, stable Pd^II complexes, compounds 3 and 4 , of two 3‐hydroxypyridine‐2‐carbaldehyde thiosemicarbazones, 1 and 2 , resp., were prepared from Li₂PdCl₄. The single‐crystal X‐ray structure of complex 3 (= [Pd( 2 )Cl]) shows that the ligand monoanion coordinates in a planar conformation to the metal via the pyridyl N‐, the imine N‐, and the thiolato S‐atoms. Intermolecular H‐bonds, π–π, and CH ? ? ? π interactions lead to a two‐dimensional supramolecular assembly. The electronic, IR, UV/VIS, and NMR spectroscopic data of the two complexes are reported, together with their electrochemical properties. A sophisticated experimental procedure was used to determine the multiple dissociation constants of the ligands 1 and 2 by UV/VIS titration.