Cage Dimer Research Articles

Solution-Dimerization of 4-Aryl-1,4-dihydropyridines

On irradiation at λ ≥ 270 nm solutions of 4-aryl-1,4-dihydropyridines 1 yield cage dimers 2 as the main products beside small amounts of anti dimers 3. 1H-NMR data and X-ray crystal structure prove centrosymmetrical properties for both dimers with axially orientated 4-aryl substituents. Irradiation with filtered light (λ > 313 nm) leads to syn and anti dimers 4 and 3 in nearly equal yields. The poor yields of anti dimers 3 on irradiation with unfiltered light are demonstrated to result from a partial cleavage back to their monomeric starting materials 1.

Cage DimericN-Acyl- andN-Acyloxy-4-aryl-1,4-dihydropyridines as First Representatives of a Novel Class of HIV-1 Protease Inhibitors

The synthesis of a series of novel cage dimeric N-acyl and N-acyloxy-4-aryl-1,4-dihydropyridines starting either from solid-state synthetic ester dimers or from monomeric 4-aryl-1,4-dihydropyridines is presented. Their biological evaluation as novel HIV-1 protease inhibitors showed the most active compounds to be 5c and 5i with inhibitory activities of 52% (50 microM) and 49% (25 microM), respectively. Within each series of N-acyl- and N-acyloxy derivatives NCOBz and NBoc groups were found to be the best substituents. Although they exhibiting only moderate activities these cage dimers hold promise as a class of novel non-peptidic HIV-1 protease inhibitors.

Solid-state photodimerization of 4-aryl-1,4-dihydropyridines studied by [formula omitted] CPMAS NMR spectroscopy

13 C CPMAS NMR spectroscopy has been applied to monitor the solid-state reaction of two different photodimerizing 4-phenyl-1,4-dihydropyridines yielding a cage dimer in one case and an anti-dimer in the other case. The spectra of the reacting monomers exhibit a magnetical inequivalence of chemically equivalent CO and C2/4 carbon atoms caused by a rotation of the pseudoaxially oriented 4-phenyl substituent out off the plane through N1, C3, C8 which could be determined by X-ray crystal structure analyses of the centrosymmetrically arranged monomers. The 13 C CPMAS NMR monitoring of the cage dimer formation proves that the reaction takes place in two steps via a syn-dimer for which a non-symmetrical structure was derived from the spectrum. The non-symmetrical structure was confirmed by X-ray crystal structure analysis of one structurally related derivative. A centrosymmetric structure for both the finally formed cage dimer and the anti-dimer of the other monitored photoreaction was proved by their spectra with one set of signals for each half of the dimers, respectively. Thus, conformational properties of the molecules as well as the symmetry of the products can be directly derived from the 13 C CPMAS NMR spectra.

Solid-state formation of centrosymmetric cage dimeric 4-aryl-1,4-dihydropyridines via non-symmetricsyn-dimers studied by13C cross-polarization magic angle spinning NMR spectroscopy

The solid-state formation of a centrosymmetric cage dimeric 4-aryl-1,4-dihydropyridine was monitored by 13C cross polarization magic angle spinning (CP/MAS) NMR spectroscopy. The spectra of the photodimerizing derivatives document the changes in symmetry during the reaction and the reaction progress. Furthermore, they clearly reflect characterizing conformational properties of the molecules. Starting from centrosymmetric pairs of monomeric molecules, dimerization proceeds to non-symmetrical syn-dimers, that subsequently cyclize to centrosymmetric cage dimers. Thus the application of 13C CP/MAS NMR spectroscopy proves an unusual symmetry breaking in solid-state photodimerization. Copyright © 1999 Society of Chemical Industry

Comparison of azacyclic urea A-98881 as HIV-1 protease inhibitor with cage dimeric N-benzyl 4-(4-methoxyphenyl)-1,4-dihydropyridine as representative of a novel class of HIV-1 protease inhibitors: a molecular modeling study.

The functional groups of cage dimeric N-alkyl substituted 3,5-bis(hydroxymethyl)-4-(4-methoxyphenyl)-1,4-dihydropyridines are similar to those of cyclic and azacyclic ureas that are potent inhibitors of HIV-1 protease of the dihydroxyethylene- and hydroxyethylene type, respectively. In the following study the conformity of common functional groups is investigated concerning their orientation in space as well as in the enzyme HIV-1 protease. Starting from X-ray crystal data of the centrosymmetric cage dimeric N-benzyl derivative with ester groups, the derivative with hydroxymethylene groups was built and a systematic conformational search was performed for the conformationally important torsion angles considering electrostatic and van der Waals interactions. From the huge number of conformations those comprising centrosymmetrical and C2-symmetrical energy minima were selected and minimized. The three remaining conformers were fitted to the azacyclic urea A-98881 selected from the HIV-1 protease enzyme-inhibitor complex using the centroids of the corresponding aromatic residues and additionally by the field fit option of the Advanced CoMFA module of SYBYL. Interestingly, the energetically most favourable one, which, additionally, possesses C2-symmetry like the active site cavity of HIV-1 protease, showed the best fit. Comparing the electrostatic potential (EP) of the latter with the EP of A-98881 the aromatic residues show excellent accordance. Slight differences in the extent of the EP were found in the areas of the hydroxymethylene groups of the cage dimer and the single hydroxy group as well as the urea carbonyl group of A-98881, respectively. In order to compare the binding possibilities to the enzyme HIV-1 protease for the cage dimer and A-98881, their interaction fields with certain probes (CH3 for alkyl, NHamide, and carbonyl, O- of COO-), representing the decisive functional groups of the active site, have been calculated using GRID and projected into the enzyme placing the structures according to the position of A-98881 in the enzyme-inhibitor complex. The strongest calculated fields of the O- probe were found near Asp 25 for both structures. Another respective conformity consists in the overlap of the fields for the NHamide probe near Ile 50 and 50' for the investigated cage dimer and A-98881.

Topochemical investigations of dimerizing 4-aryl-1, 4-dihydropyridines by X-ray crystal structure analysis

X-ray crystal structures of dimerizing 4-aryl-1,4-dihydropyridines and their solid-state irradiation products, either antidimers or cage dimers, were determined to investigate their topochemistry. The products of the solid-state reactions prove to be geometrically defined by the crystal packing of the monomers. Considering the reaction possibilities of neighbouring double bonds within the crystals of different monomers, the exclusive formation of an anti-dimer in the case of diethyl-1,4-dihydro-4-phenyl-pyridine-3,5-dicarboxylate ( 1a) and of a cage dimer via a syn-dimer in the case of dimethyl-1,4-dihydro-4-phenyl-pyridine-3,5-dicarboxylate ( 1b), can be explained by the minimum distance criterion. In both cases, the double bonds that actually react have the shortest distances from one another, i.e. 3.919(4) Å for 1a and 3.732(4) Å for 1b. On the other hand, the shortest distances between neighbouring double bonds within the light stable modification of diethyl-1,4-dihydro-4-(4-methoxyphenyl)-pyridine-3,5-dicarboxylate ( 1c) far exceed the limit.

Structure of an unusual cage dimer diol

The title compound arises from an unexpected rearrangement and oxidation. The molecules contain a center of symmetry and are held together by hydrogen bonds. The relatively strain-free molecules are closely packed with a density of 1.441 g cm−3. The compound crystallizes in space group P-1 with cell dimensions a = 8.999(3), b = 9.142(2), c = 8.625(3) A, α = 95.47(3), β = 105.06(3), and γ = 83.08(2)° There are two independent molecules per cell with each sitting on a center of symmetry.

Novel solid‐state synthesis of dimeric 4‐aryl‐1,4‐dihydropyridines

AbstractOn irradiation in the solid state the 4‐aryl‐1,4‐dihydroypridines 1 undergo [2+2] cycloadditon to centrosymmetric head‐to‐tail dimers 3 and 4a. The almost exclusive formation of the cage dimers 3 via the C2‐symmetric syn‐dimers 2 takes place in nearly quantitative yields, in contrast with the cycloaddition reaction of the anti‐dimer 4a, which is accompanied by photooxidation to pyridine 5a.

Ab initio studies of structural features not easily amenable to experiment: Part 67. The 4-21G optimized structure of a novel cage dimer, C 22H 24, and comparison with its crystal structure

The geometry of the cage dimer, C 22H 24( 1), was determined by ab initio gradient optimization on the 4-21G level. A previously described multiplicative integral approximation (MIA) was used together with the direct SCF approach. MIA is effective in determining the geometries of large molecules, at the same time achieving the accuracy of conventional SCF methods. The calculations determine the unperturbed bond distance and angle patterns of 1 with a resolution which is currently not afforded by any experimental method. The relative C'-C“ bond distances show the expected correlations with C-C'-C”-C torsions and are in good agreement with X-ray crystallographic parameters, but crystal-packing effects are noticeable at the 0.01-Å level; this is less than the packing effects on structures previously found for molecules with higher dipole moments. Thus, comparisons of this kind may provide estimates of the extent to which stronger intermolecular interactions in the crystal lead to larger deviations of the crystal structure from the isolated equilibrium structure. It is a special feature of 1 that the local geometry of the sp 2 carbons which link the two cages are asymmetric and pyramidal.

ChemInform Abstract: Structure of a Cage Dimer and a Dimer Ketone Formed via Thermal Reaction of Ethyl 3‐Phenyl‐2‐norbornadienecarboxylate with Pentacarbonyliron

ChemInformVolume 20, Issue 47 Physical Organic Chemistry ChemInform Abstract: Structure of a Cage Dimer and a Dimer Ketone Formed via Thermal Reaction of Ethyl 3-Phenyl-2-norbornadienecarboxylate with Pentacarbonyliron J. L. FLIPPEN-ANDERSON, J. L. FLIPPEN-ANDERSON Lab. Struct. Matter, Nav. Res. Lab., Washington, DC 20375, USASearch for more papers by this authorR. GILARDI, R. GILARDI Lab. Struct. Matter, Nav. Res. Lab., Washington, DC 20375, USASearch for more papers by this authorC. GEORGE, C. GEORGE Lab. Struct. Matter, Nav. Res. Lab., Washington, DC 20375, USASearch for more papers by this authorA. P. MARCHAND, A. P. MARCHAND Lab. Struct. Matter, Nav. Res. Lab., Washington, DC 20375, USASearch for more papers by this authorP. R. DAVE, P. R. DAVE Lab. Struct. Matter, Nav. Res. Lab., Washington, DC 20375, USASearch for more papers by this author J. L. FLIPPEN-ANDERSON, J. L. FLIPPEN-ANDERSON Lab. Struct. Matter, Nav. Res. Lab., Washington, DC 20375, USASearch for more papers by this authorR. GILARDI, R. GILARDI Lab. Struct. Matter, Nav. Res. Lab., Washington, DC 20375, USASearch for more papers by this authorC. GEORGE, C. GEORGE Lab. Struct. Matter, Nav. Res. Lab., Washington, DC 20375, USASearch for more papers by this authorA. P. MARCHAND, A. P. MARCHAND Lab. Struct. Matter, Nav. Res. Lab., Washington, DC 20375, USASearch for more papers by this authorP. R. DAVE, P. R. DAVE Lab. Struct. Matter, Nav. Res. Lab., Washington, DC 20375, USASearch for more papers by this author First published: November 21, 1989 https://doi.org/10.1002/chin.198947048Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume20, Issue47November 21, 1989 RelatedInformation

Structure of a cage dimer (I) and a dimer ketone (II) formed via thermal reaction of ethyl 3-phenyl-2-norbornadienecarboxylate with pentacarbonyliron

Diethyl 1,14-diphenylheptacyclo(6.6.0.- 02,6.03,13.04, ~ 1.05.9.0 ~0.14)tetradecane_2,10-dicarboxy- late (I), C32H3204, Mr=485.60, triclinic, P1, a= 9.292(2), b=11.823(2), c=13.224(3)A, t~= 66.53 (2), t= 86-80 (2), y= 68.36 (2) °, V= 1231.5(5),~ 3, Z=2, Dx=l.3OMgm -3, 2(MoKt~) = 0.71073 ./~, /t = 0.08 mm -~, F(000) = 512, T= 295K, final R =0.082, wR =0.068 for 2624 ob- served reflections. Diethyl 9-oxo-2fl,7fl-diphenyl-lfl,- 2, 3,4j~,4afl,4bfl, 5 t~,6,7,8 a, 8 aft, 9 amdodecahydro- 1,4: 5,8- dimethanofluorene-3fl,6fl-dicarboxylate (II), C33H3605, Mr=512.64, monoclinic, P2~/n, a=10.206(1), b= 17.853 (2), c= 14.940 (2)A, t= 102.50 (9) ° , V= 2657.6 (4) ,/t 3, Z = 4, D x = 1.28 Mg m -a, 2(Cu Ka) = 1.54178/~, /~ = 0.64 mm -~, F(000) = 1096, T= 295 K, final R =0.046, wR =0.057 for 3114 ob- served reflections. In (I) the cyclotetradecane cage formation occurred such that the two phenyl groups are on adjacent C atoms and all the substituents are cis with respect to one another (C-C-C-C torsion angles are -1.7 and -1.6° for the phenyl-ethoxycarbonyl neighbors and -26.9 ° for the phenyl-phenyl system). In (II) the phenyl groups are cis with respect to their adjacent ethoxycarbonyl neighbors (C-C-C-C tor- sions are -4.6 and -7.1 ° ) but are on opposite sides of the fused ring system. Introduction. As part of a detailed study of the stereochemistry and mechanism of the carbonyliron- promoted coupling of substituted norbornadienes to carbon monoxide (Marchand & Hayes, 1977; Mar- chand, Goodin, Hossain & van der Helm, 1984; Marchand, Earlywine & Heeg, 1986), the thermal reaction of Fe(CO) 5 with racemic ethyl 3-phenyl- 2-norbornadienecarboxylate (Scheme 1) has been investigated. Reactions of this type often proceed with a high degree of regio- and stereoselectivity to afford a variety of products, among which are a heptacyclic cage cyclodimer (Neely, van der Helm, Marchand &

Structure of 5-hydroxy-2,2-dimethyl-4-(p-toluenesulfonamido)-3-hexanone

such that two phenyl groups are bonded to adjacent C atoms. The geometry of this cage system is the same as that found in two earlier studies of norbornadiene cage dimers (Neely, van der Helm, Marchand & Hayes, 1976; Chow, Liu & Chao, 1985). The phenyl groups are cis to one another (C-C-C-C torsion is -26.9 °) and also cis to their adjacent ethoxycarbonyl groups (C-C-C-C torsions are -1.7 and -1.6°). In (II), the norbornadiene dimerization occurred involving a carbon monoxide molecule to form an open, rather than caged, fused ring system. The norbornadiene moieties are trans to one another across the newly formed central planar five-membered ring. Here, as in (I), the phenyl and ethoxycarbonyl moieties on adjacent C atoms are cis to one another (C-C-C-C torsions are -4.6 and -7.1°). However, the phenyl groups are on opposite sides of the fused ring system rather than on adjacent C atoms as in (I). There are no unusually close intermolecular approaches in either molecule where

Structure of a novel C22H24cage dimer

C 22 H 24 cristallise dans P1 avec affinement jusqu'a 0,048. Le compose est constitue de 2 «cages» reliees par une double liaison

Mechanism of the photodimerization of 2-naphthalenecarbonitrile and related reactions

Abstract Irradiation of 2-naphthalenecarbonitrile leads to the formation of two cage dimers which involve bonding between substituted rings in one case and a substituted and an unsubstituted ring in the other. In the presence of naphthalene, a cross-cage dimer is formed, and in the presence of anthracene (which is excited) a 9,10-[1′,4′] cross-dimer is formed. Cage naphthalene dimers are formed through two photochemical steps, the first involving the singlet excited state of 2-naphthalenecarbonitrile and a polar exciplex, and the second being the triplet-sensitized intramolecular cycloaddition of the intermediate adduct. A minor pathway from the same intermediate leads to a binaphthyl.

Photodimerization of N-benzyl-1,4-dihydronicotinamide

N-benzyl-1,4-dihydronicotinamide dimerized on irradiation with λ=365nm across 2,3 and 5,6 double bonds to give the product I which closed to centro-symmetric cage dimer IV on further irradiation with λ⩽313nm.

Photolysis and laser-excited fluorescence and phosphorescence emission of trans-glyoxal in an argon matrix at 13 K

Matrix-isolated monomers and cage dimers of trans-glyoxal in an argon matrix at 13 K photodecompose to give the same photoproducts, H/sub 2/CO and CO, when they are excited in the S/sub 2/ reverse arrow S/sub 0/ absorption region. The dimers and the monomers in minor sites are photolyzed more easily than the glyoxal monomer in major sites. No photoproducts are formed when they are excited in the S/sub 1/ reverse arrow S/sub 0/ absorption region, but both fluorescence and phosphorescence emissions are observed with the latter intensity being predominant. Glyoxal A tilde /sup 1/A/sub u/ is efficiently quenched to a tilde /sup 3/A/sub u/ in an argon matrix, with the matrix playing a role similar to that of collision partners in the gas phase.

The role of the cage dimer of formaldehyde in the photolysis of formaldehyde: Argon matrix at 12 K

Photolysis of H 2CO was carried out in an Ar matrix with different matrix ratios ( M/R). The infrared (IR) absorption spectra of the initial matrix preparation show that the matrix isolated monomers are almost exclusively present at very high dilutions ( M/R or 5000) whereas the cage dimers and higher multimers are present in significant amounts at lower dilutions. The post-photolysis IR spectra indicate that the photodecomposition of H 2CO is mainly effected with the cage dimer, and that CH 3OH and CO are formed as photoproducts. The majority of the photoproducts exist as cage dimers of CH 3OH/CO. Upon thermal annealing after photolysis, diffusion through the matrix leads to the additional formation of aggregates composed of CH 3OH/H 2CO as well as CH 3OH/CO.

The synthesis and molecular structure of a cage dimer of 7-tert-butoxynorbornadiene

The synthesis and molecular structure of a cage dimer of 7-<i>tert</i>-butoxynorbornadiene

The Photoreaction of 2,6-Diphenyl-4H-thiopyran-4-one and Its Related Compounds

Abstract The irradiation of 2,6-diphenyl-4H-thiopyran-4-one (1) or 2,6-diphenyl-4H-pyran-4-one (2) in an alcohol in the presence of oxygen gave benzoic acid and a benzoylacetic acid ester, while that of 2 in benzene or 2,6-dimethyl-4H-thiopyran-4-one (5) in various solvents gave the corresponding cage dimer, (9) or (10). No photoreaction could be observed in case of the irradiation of 1,2,6-trimethyl-4-pyridone (3) and 6-methyl-1,2-diphenyl-4-pyridone (4). A reaction mechanism via the triplet state of the substrate was also proposed.

The photodimer of p-benzoquinone

The so-called “cage dimer” pentacyclo[6,4,0,02,7,04,11,05·10]dodeca-3,6,9,12-tetraone obtained by irradiation of p-benzoquinone has been shown to have an “open” structure, and to be tricyclo[6,4,0,02,7]dodeca-4,10-diene-3,6,9,12-tetraone. This compound has been converted into biphenylene derivatives and has been reduced to the corresponding tetraol, whose tetramesylate with sodium iodide in acetone gives benzene, biphenyl, and an elusive intermediate which could be captured through the formation of Diels–Alder adducts with maleic anhydride.