Thermal Removal of Boc-Protecting Groups During Preparation of Open-Chain Polyamines

Per-N-tosylated 3,8-diaza-1,10-decanediamine (9), 4,9-diaza-1,12-dodecanediamine (spermine) (10) and 3,6,9,14,17,20-hexaaza-1,22-docosanediamine (11) were prepared by treating mono-BOC-protected, per-N-tosylated 1,2-ethanediamine (5), 1,3-propanediamine (6) and triethylenetetraamine (7), respectively, with 1,4-dibromobutane and removing the BOC-protecting groups at 100–120 °C.     

Activation and transfer of oxygen-X : A new autoxidative rearrangement of tetrahydropteridines

The structure 2a proposed by Viscontini and Okada for the autoxidation product of 5-methyl-6,7-diphenyl-5,6,7,8-tetrahydropterin 1 was found to be incorrect. Alternative structures 3a, 3b were deduced from spectroscopic data. X-ray analysis of the acetyl derivative 8 proved the oxidation product to be 2-amino-8-methyl-4,9-dioxo-cis-6,7-diphenyl-6,7,8,9-tetrahydro-4H-pyrazino(1,2-a)-s-triazine 3a. The mechanism of the rearrangement may involve an intermediate 4a-peroxy-pterin. A similar rearrangement on peroxide-level was observed for the corresponding lumazine 14.     

A Proximal Bisnitroxide Initiator: Studies in Low-Temperature Nitroxide-Mediated Polymerizations

Nitroxide-mediated "living" radical polymerization with bisalkoxyamine 2,5,5,8,8,11-hexamethyl-4,9-(1-phenylethoxy)-3,10-diphenyl-4,9-diazadodecane produces polymers of controlled length and narrow molecular weight distributions at temperatures ranging from 70 to 110 °C. Polymerizations were run successfully with styrene (St), tert-butyl acrylate (tBA), and dimethylacrylamide (DMA). EPR measurements of the homolysis of this bisalkoxyamine and monoalkoxyamine 2,2,5-trimethyl-3-(1-phenylethoxy)-4-phenyl-3-azahexane at temperatures ranging from 85 to 105 °C give rate constants for the bisalkoxyamine that are approximately twice as large as those for the monoalkoxyamine. (1)H NMR investigations of the decomposition of both alkoxyamines at 125 °C show enhanced decomposition for the bisalkoxyamine. EPR decomposition studies at 120 °C on the corresponding bis- and mononitroxides 2,5,5,8,8,11-hexamethyl-3,10-diphenyl-4,9-diazadodecane-4,9-bisnitroxide and 2,2,5-trimethyl-4-phenyl-3-azahexane-3-nitroxide also show accelerated bisnitroxide decomposition. Low-temperature EPR studies of the bisnitroxide reveal an unusually strong radical-radical interaction, suggesting enhanced stabilization of the intermediate mononitroxide formed during polymerization by interaction with the proximal N-alkoxyamine. The transient mononitroxide is postulated to be stabilized by delocalization of the unpaired electron density over five atoms.     

Stereoselective Mannich reactions catalyzed by Tröger’s base derivatives in aqueous media

A Tröger’s base derivative (5,12-dimethyl-3,10-diphenyl-1,3,4,8,10,11-hexaazatetracyclo [6.6.1.0^2,6.0^9,13]pentadeca-2(6),4,9(13),11-tetraenes) was used as an efficient catalyst for the three-component Mannich reactions of aromatic aldehydes and aromatic amines with ketones in water at room temperature. This rapid reaction afforded the corresponding β-amino ketones in good yields with excellent stereoselectivity.     

Synthesis of a new chiral cyclic aminal derived from rac-1,2-propanediamine

The cyclic aminal 4,9-dimethyl-1,3,6,8-tetraazatricyclo[4.4.1.1^3,8]dodecane 4c was synthesized by the reaction of commercial rac-1,2-propanediamine with paraformaldehyde in an aqueous solution. ¹H NMR analysis clearly revealed that the compound is chiral and racemic with an axis of chirality. To our knowledge, this is the first example of an azaadamantane derivative having axial chirality. This aminal was used in a Mannich type reaction with p-chlorophenol yielding 2,2′-[(4-methylimidazolidine-1,3-diyl)dimethanediyl]bis(4-chlorophenol) 7 as a racemic mixture. The crystal structure of 7 was determined by single X-ray diffraction analysis.     

Synthesis and characterization of novel (<Emphasis Type="Italic">E</Emphasis>,<Emphasis Type="Italic">E</Emphasis>)-dioxime and its mono- and polynuclear metal complexes containing azacrown moieties

The novel (E,E)-dioxime,7,8-bis(hydroxyimino)-1,14-bis(monoaza[8]crown-6)-benzo[f]-4,11-dioxa-1,14-diazadecane[7,8-g]quinoxaline (H₂L), has been synthesized by the reaction of 6,7-diamino-1,12-bis(monoaza[18]crown-6)benzo[f]-4,9-dioxa-1,12-diazadecane (4) which has been prepared by the reduction of 6,7-dinitro-1,12-bis(mono-aza[18]crown-6)benzo[f]-4,9-dioxa-1,12-diazdecane (3) and cyanogendi-N-oxide. Mononuclear Ni^II and Cu^II complexes of H₂L have a metal:ligand ratio of 1:2 and the ligand coordinates through two hydroxyimino nitrogen atoms, as do most of the (E,E)-dioximes. The hydrogen-bridged Ni^II complex was converted into its BF ₂ ⁺ capped anologue by the reaction with BF₃ · Et₂O. The reaction of the Cu^II complex with 2,2′-dipyridyl as an end-cap ligand gave the homotrinuclear complex. Structures for the ligand and its complexes are proposed in accordance with elemental analysis, magnetic susceptibility measurements, ¹H, ¹³C-n.m.r, IR and MS spectral data.     

MICROENVIRONMENT OF AROMATIC HYDROCARBONS EMPLOYED AS FLUORESCENT PROBES OF LIPOSOMES

Abstract— The enhancement of weakly allowed vibronic transitions in the fluorescence spectra of pyrene, 1,12-benzoperylene and naphthalene, which we previously found to be the result of the reduction of the molecular symmetry caused by ground state complex formation with polar solvents, has been employed in the present work to study the microenvironment of these aromatic hydrocarbons when incorporated as fluorescent probes into egg phosphatidylcholine and dipalmitoyl phosphatidylcholine liposomes. The probes are found to interact and form ground state molecular complexes with polar groups of the liposomes. For egg phosphatidylcholine the degree of enhancement is matched by that in butanol, methanol and dioxane for the three probes, respectively. For dipalmitoyl phosphatidylcholine the matching solvents are ethanol, dimethylformamide and dioxane below the phase transition, while they are ether, methanol and dioxane above it. Thus, above the phase transition pyrene and 1,12-benzoperylene penetrate further into the liposomes, while naphthalene retains approximately the same location.     

Reactions of 3,10-epoxycyclo[10.2.2.0.0]hexadeca-4,6,8,13-tetraene: a new intramolecular 1,5-oxygen migration

Bromination of 3,10-epoxycyclo[10.2.2.0^2,11.0^4,9]hexadeca-4,6,8,13-tetraene gave 13-bromo-11-oxapentacyclo[8.7.0.0^2,4.0^12,17]heptadeca-4,6,8-triene-3-ol, 12-bromo-1,2,3,4-tetrahydro-1,4-ethano-antracen-11-ol, 13-hydroxy-3,14-dibromotetracyclo[10.2.2.0^2,11.0^4,9]hexadeca-2,4,6,8,10-pentaene, and 13-hydroxy-3,10,14-tribromotetracyclo[10.2.2.0^2,11.0^4,9]hexadeca-2,4,6,8,10-pentaene by cleavage of the carbon–oxygen bonds and intramolecular 1,5-migration of the oxygen atom of 1,4-epoxide. Reactions of epoxide 14,18-dioxahexacyclo[10.3.2.1^3,10.0^2,11.0^4,9.0^13,15]octadeca-4,6,8-triene obtained from 3,10-epoxycyclo[10.2.2.0^2,11.0^4,9]hexadeca-4,6,8,13-tetraene gave also similar products, in acidic media. Compound 3,10-epoxycyclo[10.2.2.0^2,11.0^4,9]hexadeca-4,6,8,13-tetraene was converted into tetracyclo[10.2.2.0^2,11.0^4,9]hexadeca-2(11),3,9-triene in two ways. The reactions, especially intramolecular oxygen migration, are discussed.     

Metal-ammonia reduction—XIV : Fluoranthene: Correlation of primary product structure with HMO theoretical prediction

Reduction of fluoranthene with lithium in liquid ammonia affords the previously undetected theoretically predicted product 3,10b-dihydrofluoranthene (3) in good yield, accompanied by minor amounts of the 2,3-dihydro isomer (2) which is shown to arise via base-catalyzed isomerization of 3. Analogous reductive methylation of fluoranthene with methyl bromide affords either 10b-methyl-3,10b-dihydrofluoranthene (4) or 3,10b-dimethyl-3,10b-dihydrofluoranthene (5), as the major product, depending upon use of lithium or sodium. Mechanism and stereochemistry of these transformations are discussed. NMR spectral analysis of the 3,10b-dihydrofluoranthene derivatives is reported; these compounds are distinguished by an unusual 1,4-cyclohexadiene ring system locked in a relatively rigid flattened boat conformation.     

1,1,4,4-Tetranitrobutane-2,3-diol and its derivatives. 4. Study of the reaction of 1,1,4,4-tetranitrobutane-2,3-diol with N-(methoxymethyl)-2-fluoro-2,2-dinitroethylamine; synthesis and crystalline structure of 1,12-difluoro-1,1,3,5,5,8,8,10,12,12-decanitro-3,10-diazadodecane-6,7-diol dinitrate

A two-step synthesis has been proposed to obtain 1,12-difluoro-1,1,3,5,5,8,8,10,12,12-decanitro-3,10-diazadodecane-6,7-diol dinitrate, starting from 1,1,4,4-tetranitrobutane-2,3-diol and N-(methoxymethyl)-2-fluoro-2,2-dinitroethyl-amine, followed by nitration of the Mannich base formed. An x-ray-diffraction investigation of the dinitrate obtained was carried out.Insitute of Chemical Physics, Russian Academy of Sciences, 142432 Chernogolovka. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 3, pp. 671–675, March, 1992.     

A facile total synthesis of rutaecarpine

The indoloquinazoline alkaloid rutaecarpine has been synthesized efficiently by employing 9,10,11,12-tetrahydro-4H-pyrido[2,1-b]quinazoline-4,9-dione (4) as a key intermediate, which was prepared by adapting a Dieckmann condensation-decarboxylation sequence from quinazolinone diester 6.     

Twista-4,9-diene. Preliminary communication

A synthesis of twista-4,9-diene ( 17 ) from tricyclo[4.3.1.0^3,8]dec-4-en-10-one ( 2 ) is described.     

A new class of nitrogen based chiral ligands: 2H-1,3-benzoxazines. Ligand synthesis, X-ray structural studies and asymmetric catalysis

A new class of chiral ligands, e.g., (−)-9, based on the benzoxazine nucleus, has been designed and synthesized in three steps from the commercially available starting materials salicylamide and (−)-menthone. Application of (−)-9 in the palladium catalyzed-allylic substitution of 1,3-diphenyl-2-propenylacetate with dimethyl malonate gave enantioselectivities of up to 62%ee. Ees of 42% and 20% in asymmetric hydrosilylations and diethylzinc additions, respectively, were also obtained.     

Head-to-head polymers — XXXII: Toward head-to-head poly(α-methylstyrene): Synthesis of 2,3-dimethyl-2,3-diphenylbutanediol-1,4-ditosylate and 1,4-diphenyl-2,3-dimethylbutadiene-1,3

2,3-Dimethyl-2,3-diphenylbutanediol-1,4-ditosylate (7) was synthesized starting from 2-phenylpropionic acid (1). The acid chloride was brominated and transformed into methyl 2-phenyl-2-bromo-propionate (4) which was coupled with a zinc/copper couple to dimethyl 2,3-dimethyl-2,3-diphenylsuccinate (5). Reduction with lithium aluminum hydride to 2,3-dimethyl-2,3-diphenylbutanediol-1,4 (6) was followed by tosylation. The tosylate 7 a mixture of the meso and racemic compounds, could be separated into the pure isomers,a m. p. 170 °C andb m. p. 121 °C. The mixture of each individual pure compound, when treated with tetraalkyl-ammonium bromide, did not give the expected 2,3-dimethyl-2,3-diphenyl-1,4-dibromobutane (9) but rather 1,4-diphenyl-2,3-dimethylbutadiene-1,3 (8). The identity of the compound was established by independent unequivocal synthesis, the comparison of spectral characteristics, and mixed melting point.     

Absorption spectra of amorphous organic films

Using a low-temperature evaporation technique, amorphous-state films of naphthacence, perylene, coronene and 1,12-benzoperylene were prepared, and their absorption and fluorescence spectra were measured. The obtained results are discussed and compared with the corresponding crystal-state spectra.     

Synthesis and characterization of novel triazenes from the reaction of the cyclic aminal 1,3,6,8-tetraazatricyclo[4.3.1.1]undecane (TATU) with diazonium ions

The reaction of the cyclic aminal 1,3,6,8-tetraazatricyclo[4.3.1.1^3,8]undecane (TATU, 4) with diazonium salts resulted in the formation of a new series of bis-triazenes, namely 3,8-bis[(4-methoxyphenyl)diazenyl]-1,3,6,8-tetraazabicyclo[4.3.1]decane 6a, 3,8-bis[(2-methoxyphenyl)diazenyl]-1,3,6,8-tetraazabicyclo[4.3.1]decane 6b, 3,8-bis(p-tolyldiazenyl)-1,3,6,8-tetraazabicyclo[4.3.1]decane 6c. When aniline derived diazonium salt 5d was coupled with TATU, 3,8-bis(phenyldiazenyl)-1,3,6,8-tetraazabicyclo[4.3.1]decane 6d and bis[1,5-bis-((E)-phenyldiazenyl)-1,3,5-triazepan-3-yl]methane 7 were obtained. These compounds were characterized by HR-MS, ¹H and ¹³C NMR and 2D-NMR. Additionally, the structure of compound 7 was confirmed by X-ray crystallography.     

Synthesis of 4,4′-bipentacyclo[5.4.0.02,6.03,10.05,9]undecane

A new bi-cage hydrocarbon, 4,4′-bipentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane (12) was designed based on a strategy to construct two cages simultaneously from one key molecule scaffold. Thus 12 was conveniently synthesized from 5,5′-bi(cyclopentadiene) (9) through a three steps synthetic route in 23% overall yield. The new bi-cage hydrocarbon has high density (1.2322 g/cm³) and high volumetric heat of combustion (51.670 MJ/L).     

New electron-accepting quinoxalinothiadiazole-containing heterocycles as promising building blocks for organic optoelectronic devices

Two novel quinoxalinothiadiazole-containing dibromides—4,9-dibromo-6,7-bis(9,9-didodecyl7-fluoro-9H-fluoren-2-yl)[1,2,5]thiadiazolo[3,4-g]quinoxaline (11) and 4,9-dibromo-6,7-bis(9,9-didodecyl-5,7-difluoro-9H-fluoren-2-yl)[1,2,5]thiadiazolo[3,4-g]quinoxaline (19)—have been synthesized, which are promising strong electron-accepting building blocks for preparing highly efficient narrow-bandgap D–A conjugated polymers. The composition and structure of monomers 11 and 19 have been proved by elemental analysis data, IR spectroscopy, and ¹H and ¹³C NMR.     

Base-promoted rearrangement of cage α-haloketones—II : 12-oxa-3,5,9,10-tetrachlorohexacyclo[5.4.1.02,6.03,10.05,9.08,11]-dodecane-4-one

A synthesis of 12-oxa-3,5,9,10-tetrachlorohexacyclo[5.4.1.0^2,6.0^3,10.0^5,9.0^8,11]dodecane-4-one (6) from 4,4-dimethoxy-2,3,5,6-tetrachloropentacyclo [[5.4.0.0^2,6.0^3,10.0^5,9]undecane-8,11-dione (1) is described. Reaction of 6 with sodium hydroxide in refluxing benzene, toluene, or tetrahydrofuran affords 11-oxa-3,4,5-exo-6-tetrachloropentacyclo [[6.2.1.0^2,7.0^4,10.0^5,9]undecane-endo-3-carboxylic acid (7a, 80·2% yield). The corresponding reaction of 6 with refluxing aqueous sodium hydroxide solution affords 4,12-dioxa-8,11-dichlorohexacyclo-[5.4.1.0^2,6.0^3,10.0^5,9.0^8,11]dodecane-1-carboxylic acid (8a, 66·5% yield). A mechanism which accounts for the formation of 7a and 8a from 6 is presented.     

Novel tetradentate diamine dioxime ligands: synthesis,characterization and in vivo behavior of their 99mTc‐complexes

Two novel diamine dioxime ligands, 4,7‐diaza‐3,8‐diethyldecane‐2,9‐dione bis oxime (3) and 4,9‐diaza‐3,10‐diethyldodecane‐2,11‐dione bis oxime (5), were synthesized in order to develop new brain perfusion imaging agents, based on ^99mTc(V)‐complexes. The synthesis involved condensation of 2‐hydroxyimino‐3‐pentanone with appropriate diamine in protic solvent which afforded the bis imine adducts. Subsequent reduction of imine functional groups yielded a diastereoisomeric mixture of 3 and 5. UV–visible, IR, ¹H NMR, ¹³C NMR and elemental analysis were used to characterize the structures of the synthesized compounds. ^99mTc‐complexes of both diamine dioximes were prepared and radiolabeling conditions optimized to give the maximum yield. Physicochemical parameters of the labeled complexes as well as and their biodistribution in rats were investigated. Both compounds (3 and 5) formed ^99mTc‐complexes with a net charge of zero, determined by electrophoresis. The resultant lipophilic ^99mTc‐complexes of 3 and 5 were readily formed at pH ~9.0 within 10 min at room temperature with yields of 90% and 95%, respectively. The ^99mTc‐3 complex was found to be stable within 1 h, while ^99mTc‐5 was stable for a few hours. A significant brain uptake of ^99mTc‐3 (2.1% injected dose) and ^99mTc‐5 (1.8% injected dose) complexes, 2 min after injection, is in accordance with their lipophilicity. The present study suggests that both ligands are promising candidates as new ^99mTc‐based brain‐imaging agents. Copyright © 2012 John Wiley & Sons, Ltd.