On the polyenic character of anti-bridged[14]annulene. The structure of anti-1,6:8,13-bis(difluoromethano) [14]annulene at 200K

The X-ray crystal structure determination ofanti-1,6:8,13-bis(difluoromethano) [14]annulene (1) at 200 K is described. The structure has been solved by direct methods, and least-squares refinement based on 1716 reflections of non-zero weight yielded a finalR index of 0.046. The molecular structure of1 appears to be polyenic, as expected from a comparison with the structures of previously studiedanti-bridged[14]annulenes, and in particular confirms conclusions previously reported from a study of the stucture ofanti-1,6:8,13-biscarbonyl [14]annulene.     

Conformational analysis—XIII: Syn and anti [3.2]-, [3.3]-, [4.2]-, and [4.3]-metacyclophanes

While in [3.3]metacyclophane (19) the aromatic rings preferentially adopt the syn arrangement, its lower and higher homologues, i.e. [2,2]-, [3.2]-, [4.2], and [4.3]-metacyclophane (1, 6, 26 and 30), adopt the anti conformation. Substituted [m,n]metacyclophanes do not necessarily behave similarly to the parent hydrocarbons. Substituted compounds exhibiting a different conformation are [3.2]metacyclophane-1,11-dione (7) (syn), [3.3]metacyclophane-2,11-dione (24) and the corresponding bis[propylene thioacetal] (25) (anti), [4.2]metacyclophane-2,12-dione (27) (syn), and [4.3]metacyclophane-2,13-dione (31) (syn). Thus, the solution conformation of an [m.n]metacyclophane is sensitive both to chain length [m.n.] of the bridges and substitution. The ring inversion barriers determined by variable temperature ¹H NMR decrease with increasing length of the bridges and qualitatively correlate with the transanular strain present in the pertinent system.     

Nitroxydes—LXIV : Decomposition thermique de radicaux libres nitroxydes isoquinuclidiniques

Pyrolysis of 1,3,3-triméthyl-2-azabicyclo[2,2,2]octan-5-one-2-oxyl 5 leads to N-hydroxy-1,3,3-trimethyl-2-aza bicyclo[2,2,2]octan-5-one 6 and N-hydroxy-4,7,7-trimethyl-6-aza bicyclo[3,2,1]oct-3-ene-2-one 7. Under the same conditions, 1,3,3,7-anti-tetramethyl-2-aza bicyclo[2,2,2]octan-5-one-2-oxyl 9 leads to N-hydroxy-1,3,3,7-anti-tetraméthyl-2-aza bicyclo[2,2,2]octan-5-one 13 and N-hydroxy 4,5,7,7-tetramethyl-6-aza bicyclo[3,2,1]oct-3-ene-2-one 14, while 1,3,3,7-syn-tetramethyl-2-aza bicyclo[2,2,2]octan-5-one-1-oxyl 10 is stable. Kinetic studies show that the reaction proceeds by an autocatalytic process, probably involving an ionic mechanism.     

Structural properties of five- and six-layered [3.3]metacyclophanes

We performed X-ray structural analyses of the five- and six-layered [3.3]metacyclophanes (MCPs) 1 and 2 and the six-layered [3.3]MCP tetraone 3. In the solid state, the MCP moieties of 1, 2, and 3 adopt different conformations from those of the free MCPs in solution. In the five-layered [3.3]MCP 1, all the [3.3]MCP moieties adopt anti (chair/boat) conformations. In the six-layered [3.3]MCP 2, two three-layered [3.3]MCPs are connected by a [3.3]MCP in the anti conformation with completely parallel benzene rings. In the six-layered [3.3]MCP tetraone 3, the outer [3.3]MCP moieties and diones adopt general syn and anti geometries, respectively. However, the inner [3.3]MCP moiety adopts an anti geometry. Based on density functional theory (DFT) calculations, the most stable conformers of 1, 2, and 3 are syn (chair/chair) in the [3.3]MCP moieties and anti (twist boat/twist boat) in the dione moieties.     

An expedient synthesis and conformational features of acylhydrazone macrocycles derived from tartaric acid: evidence of water and π aromatic hydrogen bond interactions

Tartaric acid dihydrazides with acetal protected hydroxy groups react with terephthalaldehyde to preferentially form [2+2] bisacylhydrazone macrocycles. The structures of these macrocycles display all anti N–N and CN bonds. Both trans- and cis-C(O)–NH bonds are present in the macrocycle thus allowing the formation of a rather compact macrocyclic structure. The structures of the acylhydrazone macrocycle are shown to be different in the crystal and in the isolated molecule due to the structure determining role of water included in the crystal lattice: in the former all of the OC–C–H bonds are anti, while in the latter both syn- and anti-bonds are present. Both the non-planarity of the bisacylhydrazone molecules and their chiral interchromophoric interactions contribute to the rotatory power of the molecule. The low-temperature X-ray crystal structure of this compound provides direct evidence for hydrogen bonding between water and the aromatic π-electrons in the solid state.     

Two new water-soluble derivatives of 1,3,5-triaza-7-phosphaadamantane (PTA): Synthesis,characterization, X-ray analysis and solubility studies of 3,7-diformyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane and 1-pyridylmethyl-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1]decane bromide

Two water-soluble phosphines, 3,7-diformyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (1, DFPTA) and 1-pyridylmethyl-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1]decane bromide (2, [pymePTA]Br), have been respectively, prepared by reacting 1,3,5-triaza-7-phosphaadamantane (PTA) with formic anhydride and bromomethylpyridine. Compound 1 is only the second acyl derivative of PTA to be prepared while 2 is only the second derivative of PTA reported that contains an aromatic appendage. Both compounds were characterized by elemental analysis, FAB-MS, ¹H, ¹³C, and ³¹P NMR spectroscopy, and single crystal X-ray diffraction. This analysis showed that the formamide groups of 1 were in an anti confirmation in solution but in a syn confirmation in the solid state. The solubilities of 1 and 2 were examined in common organic solvents and water. It was found that 1.1 M aqueous solutions of 1 could be prepared while 2.4 M solutions of 2 were produced. The greater solubility of 2 was likely due to its ionic nature.     

Synthesis and structure characterization of unsymmetrical oxacalix[2]benzene[2]pyrazines

The synthesis of two unsymmetrically linked oxacalix[2]benzene[2]pyrazines (1 and 2) is described. X-ray single crystal structure analysis revealed a highly distorted 1,3-alternate conformation of compound 1 (containing ortho- and meta-diphenol components) and a distorted boat conformation of compound 2 (containing meta- and para-diphenol components). Oxacalix[2]benzene[2]pyrazine containing both ortho- and para-diphenol components was not obtained via similar synthetic strategy.     

S-shaped para-Quinodimethane-Embedded Double [6]Helicene and Its Charged Species Showing Open-Shell Diradical Character

Helicenes and extended helical π-conjugated compounds have been widely studied, but most of the systems contain only aromatic benzene or heterocyclic rings, showing local aromatic character. Herein, new S-shaped double [6]helicene 1 , which has two embedded para-quinodimethane (p-QDM) units, is reported. Due to the existence of a proaromatic quinoidal substructure, it has open-shell diradical character. Its model compound, C-shaped single [6]helicene 2 containing one p-QDM unit, was also synthesized and compared. Their ground-state structures and electronic properties were systematically studied by a combination of various experimental methods assisted by theoretical calculations. Compound 1 has a double-helical structure in the crystal, with the two terminal [6]helicene units bent in opposite directions (i.e., anti form). However, an anti/syn isomerization process with a moderate interconversion energy barrier was observed on the NMR timescale. Compound 1 shows amphoteric redox behavior. It also exhibits open-shell diradical character (y₀=12.1 %) and a small singlet–triplet gap. On the other hand, compound 2 has a typical closed-shell nature. The dication and dianion of 1 also show open-shell diradical character. The dianion of 2 and the tetraanion of 1 exhibit similar electronic structures to their respective isoelectronic structures, that is, [6]helicene and a double [6]helicene. This work provides some insights into the design and synthesis of stable helical π systems with open-shell diradical character and magnetic activity.     

A new chemoenzymatic synthesis of d-cloprostenol

A new chemoenzymatic synthesis of d-cloprostenol based on the biocatalytical resolution of anti-2-oxotricyclo[2.2.1.0]heptan-7-carboxylic acid 1 has been developed. The resolution was attempted by different approaches: esterification or reduction of the acid and hydrolysis or reduction of the corresponding esters. The most efficient method proved to be the reduction of the propyl esters of 1 catalysed by the yeast Kluyveromyces marxianus, which allowed for the recovery of the enantiomerically pure ester of anti-2-oxotricyclo[2.2.1.0]heptan-(R)-7-carboxylic acid (R)-3 at 60% molar conversion of 3.0 g/l of racemic substrate acid under optimised conditions. anti-2-Oxotricyclo[2.2.1.0]heptan-(R)-7-carboxylic acid was obtained by alkaline hydrolysis and employed for the synthesis of d-cloprostenol.     

Intramolecular rearrangement of 1,3-bistriflate ester of thiacalix[4]arene to 1,2-counterpart: an efficient di-O-protection method for the stereoselective synthesis of anti-1,2-diethers

A net anti-selective dialkylation of the proximal hydroxy groups of thiacalix[4]arene 2 is achieved for the first time via the initial protection of the two proximal hydroxy groups of compound 2 with Tf moieties by intramolecular rearrangement of easily preparable 1,3-bistriflate ester 3 to 1,2-counterpart 4, followed by anti-selective dialkylation of the remaining hydroxy groups with alkyl halides or under the Mitsunobu conditions and subsequent removal of the Tf moieties.     

Synthesis and structure of a chiral areno-bridged [2.4]metacyclophane

The reductive coupling reaction of 1,4-bis(3-acetyl-5-tert-butyl-2-methoxyphenyl)butane 3 was carried out using TiCl₄-Zn in pyridine followed by a McMurry coupling reaction to afford the compounds anti and syn 1,2-dimethyl[2.4]MCP-1-ene 4. Bromination of 4 with BTMA-Br₃ in dry CH₂Cl₂ afforded the interesting compound 1,2-bis-(bromomethyl)-5,15-di-tert-butyl-8,18-dimethoxy[2.4]MCP-1-ene 6 and consecutive debromination with Zn and AcOH in CH₂Cl₂ solution afforded the stable solid 5,15-di-tert-butyl-8,18-dimethoxy-1,2-dimethylene[2.4]MCP 7 in 89% yield. Compound 7 was conveniently employed in a Diels–Alder reaction with dimethyl acetylenedicarboxylate (DMAD) to provide 2-(3′,6′-dihydrobenzo)-5,15-di-tert-butyl-8,18-dimethoxy[2.4]MCP-4′,5′-dimethylcarboxylate 8 in good yield. Diels–Alder adduct 8 was converted into a novel and inherently chiral areno-bridged compound [2.4]MCP 9 by aromatization. The chirality of the two conformers was characterized by circular dichroism (CD) spectra of the separated enantiomer which are perfect mirror images of each other.     

Synthesis of benzimidazole derivatives via reaction between aromatic amines and aldehydes: Structure determination and theoretical insights

The condensation reaction between primary amine and aromatic aldehyde or ketone ubiquitously synthesizes –C=N- function that appears in the Schiff bases. Presence of ortho –NH/NH₂ group may form a cyclic product which is further oxidized to generate –C=N- function. Herein, two quinoline based cyclic benzimidazole compounds, namely, 2-[1-(Phenyl-pyridin-2-yl-methyl)-1H-benzoimidazol-2-yl]-quinoline (L5) and 2-[1-(Phenyl-pyridin-2-yl-methyl)-1H-benzoimidazol-2-yl]-quinolin-8-ol (L6) are synthesized from o-phenylenediamine derivative [N¹-(phenyl(pyridin-2-yl)methyl)benzene-1,2-diamine] (L) via condensation followed by in-situ dehydrogenation. The structures of the products have been confirmed by the single crystal X-ray diffraction measurement and other physicochemical data. The intra- and intermolecular H-bonding, C–H ^… π interactions in the structures instigate supramolecular self-assembly. The DFT computation has been attempted to explain the formation of energy minimized cyclic product out of acyclic counterpart; the meticulous comparison of the present theoretical outcomes with that of previously reported o-phenylenediamine derivatives, further supports the formation of energy minimized products.     

Ultrasonic-bath-assisted preparation of mononuclear copper(I) thiosemicarbazone complex particles: Crystal structure,characterization and antimicrobial activity

Particles of the copper(I) thiosemicarbazone complex [Cu(Brcatsc)(PPh3)2Cl]·CH3CN (1), Brcatsc = 2-bromo-3-phenylpropenalthiosemicarbazone, were synthesized by an ultrasonic-bath-assisted method and characterized by elemental analyses, NMR (¹H, ¹³C, and ³¹P) and FT-IR spectroscopies, X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). The thermal stability of 1 was studied by thermal gravimetry analysis and its structure was determined by single crystal X-ray diffraction. The compound 1 is a mononuclear complex with the copper(I) ion coordinated in a distorted tetrahedral geometry by one S atom of Brcatsc, two P atoms of two PPh₃, and one Cl atom. The complex involves the Brcatsc thiosemicarbazone ligand in an S monodentate bonding mode. The antibacterial activity of the ligand and its copper(I) complex was studied against two gram-positive (Staphylococcus aureus and Enterococcus faecalis) and two gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria.     

Structural properties of charge-transfer complexes of four- and five-layered [3.3]metacyclophanes

In the solid state, the cyclophane (CP) moieties of the charge-transfer (CT) complexes of four- and five-layered [3.3]metacyclophanes (MCPs) 1 and 2 with tetracyanoethylene (TCNE) take different conformations from those in the solid state of the free MCPs. In the four-layered [3.3]MCP 1-TCNE complex, the CP moiety takes an s-shaped syn-anti-syn geometry, whereas the inner three benzene rings take the all-syn geometry and the two outer [3.3]MCP moieties have deformed anti-conformations in the five-layered [3.3]MCP 2-TCNE complex. In the crystal-packing diagrams of each complex, intermolecular CH/π-type interactions are observed between adjacent molecules.     

Stereospecific mono- and difluorination of the C7-bridge of norbornenes

Fluorinated norbornenes are very desirable monomers in the semiconductor and high-temperature polyimide industries. We describe herein a synthetic strategy for the stereospecific mono- or difluorination of the C₇-carbon in norbornene systems beginning with 7-ketonadic anhydride 1. In particular, anti-7-fluoro methyl diester 4 and its 7,7-difluoronadic analog 7 can be prepared from 1 in 3 or 4 steps: saponification, reduction (for 4), esterification, fluorination with DAST. In addition, anti-7-fluoro-syn-7-fluoromethylnadic diester 16 is obtained from epoxide 14, and dimethyl 7,7-difluorobicyclo[2.2.2]oct-5-ene-2,3-dicarboxylate (17) from ketone 15. Anchimeric assistance of the norbornene double bond guides the introduction of attacking fluoride anions stereospecifically anti to the olefinic linkage.     

Synthesis of 9-nitro-5H-spiro[benzo[b]tetrazolo[1,5-d][1,4]oxazepine-4,2′-oxirane] via an unusual ring-expansion

Attempted cyclization of (4-(hydroxymethyl)-8-nitro-4H-benzo[b]tetrazolo[1,5-d][1,4]oxazin-4-yl)methyl 4-methylbenzenesulfonate 2 did not give the expected spirooxetane product 1, but instead provided 9-nitro-5H-spiro[benzo[b]tetrazolo[1,5-d][1,4]oxazepine-4,2′-oxirane] 3via an unusual ring-expansion process. The structure of compound 3 was confirmed by single-crystal X-ray crystallography. The spiroepoxide (oxirane) in compound 3 could be ring-opened with a variety of nucleophiles to give products of potential interest to medicinal chemists.     

Selective crown ether based macrocyclization: a model case study from N,N-bis(2-hydroxyalkylbenzyl)alkylamine

A model case of selective crown ether based macrocycles, i.e., [1+1] or [2+2] macrocycles, obtained from a simple reaction of N,N-bis(2-hydroxyalkylbenzyl)alkylamine, HBA, and ditosylated compounds is proposed. For HBA with the methyl group at ortho and para positions, and at N atom, 1, the reaction between this derivative and the ditosylated compound with three, four, five, or eight atom chain length gives only a [1+1] macrocycle. For HBA with the methyl group at ortho and para positions, but a cyclohexyl group at N atom, 2, the reaction gives both [1+1] and [2+2] macrocyclic types when reacting with the ditosylated compound. The present work indicates that the structure of HBA induces selective macrocyclization to provide both [1+1] and [2+2] macrocycles.     

DBU induced formation of 8-bromoguanosine dimer with three hydrogen bonds between the GG− base pairs

Upon hemideprotonation of 8-bromoguanosine (8-BrG) at the N1 position, induced by DBU, the adduct [8-BrG][8-BrG]^?[DBU–H]⁺ was formed. Slow evaporation of the 8-BrG methanol solution, in the presence of 0.5 equiv of DBU, yielded two polymorphic structures (1 and 2), where a neutral [8-BrG] (A) and N1 deprotonated, anionic 8-bromoguanosine [8-BrG]^? (B) were joined together through three intermolecular hydrogen bonds involving O6, N1 and C2–NH₂ sites. Such pairing gave planar GG^? dimers as the basic motif of crystal packing in both polymorphs. Both neutral and deprotonated guanosine molecules in the structure of 1 had the ribose units in a syn conformation. In the structure of polymorph 2, the N1 deprotonated guanosine molecule (B) retained the syn glycosidic conformation, while the non-deprotonated guanosine molecule (A) adopted the natural anti conformation of the ribose unit with respect to the nucleobase. Ribose rings revealed different puckering; only those of deprotonated molecules 1B and 2B possessed the usual C2′-endo envelope conformation. Crystal packing in both structures was guided by the highly complex H-bonded pattern. The CSD was searched for related structures, which are discussed with reference to polymorphs 1 and 2. ¹H and ¹³C NMR spectroscopic evidence is provided showing that the three H-bonded adduct [8-BrG][8-BrG]^?[DBU–H]⁺ was also formed in the highly H-bond competitive DMSO solution.     

Synthesis,structure, and conformation of terphenylene-derived azacalix[4]aromatics

Several novel azacalix[4]aromatics constituting terphenylene units have been synthesized via sequential nucleophilic aromatic substitution reactions of 5′-t-butyl-(1,1′:3′,1″-terphenyl)-3,3″-diamine 9 and 5′-t-butyl-(1,1′:3′,1″-terphenyl)– 4,4″-diamine 11 with 1,5-difluoro-2,4-dinitrobenzene and cyanuric chloride, respectively. The bridging –NH– functions of the tetra-nitro substituted azacalix[2]arene[2]terphenylenes 1 and 2 have been transformed to the corresponding –N(CH₃)– bridged azacalix[2]arene[2]terphenylenes 3 and 4 via N-alkylation. Single crystal X-ray analysis revealed that the terphenyl-3,3″-diamine derived azacalix[2]terphenylene[2]triazine 5 adopts a distorted chair conformation in the solid state, and the terphenyl-4,4″-diamine derived azacalix[2]terphenylene[2]triazine 6 was found to adopt a 1,3-alternate conformation.     

The configuration and conformation of isogermacrone. The significance of crossed conformations in olefinic cyclisations

The 9,10-double bond of isogermacrone was assigned the Z configuration based on¹HNMR nOe measurements and the ¹³CNMR shifts of the methyl groups. An X-ray crystal structure determination verified this conclusion and the structure of isogermacrone was shown to be (2Z, 7E)-3,7-dimethyl-10(1-methylethyl-idene)-2,7-cyclodecadien-1-one (1). The molecule crystallised in an anti conformation, which according to ¹HNMR is the predominant conformation in solution at room temperature.¹H NMR spectroscopy revealed the presence of syn and anti conformers in the ratio 1:2 at about -60°. The stereochemistry of the base-induced formation of isogermacrone 1 from germacrone 2 and that of the transannular cyclisation of isogermacrone are discussed.