On triazoles. XXV. The reaction of methyl (5-amino-3-Q-1H-1,2,4-triazolyl)dithiocarbonates with amines

Different “functionalised” triazolylthioamides 3 and -thioureas 4 were synthesised. The ring closure of the ω-hydroxyalkylthioamides 3/2–5 led to the corresponding 2-thiazoline 5/2–4 and 5,6-dihydro-4H-1,3-thiazine 5/5 derivatives, respectively. Unexpectedly, the ring closure of the corresponding 2,2-dimethoxyethyl derivative 3/18 led depending on the reaction conditions to a thiazole derivative 6 or to its 1,2,4-triazolo[3,4-b]-1,3,5-triazepin-5(9H)-thione isomer 7 representing a novel ring system. To corroborate its structure 7 was methylated to the corresponding S-methyl derivative 8 . Spectroscopical evidence is given for the structure of derivatives 3–8 obtained.     

On triazoles. VIII The reaction of 5-amino-1,2,4-triazoles with ethyl 2-cyano-3-ethoxyacrylate and 2-cyano-3-ethoxyacrylonitrile

The reaction of different 5-amino-3-Q-1H-1,2,4-triazoles 1 with ethyl 2-cyano-3-ethoxyacrylate ( 5a ) and 2-cyano-3-ethoxyacrylonitrile ( 5b ) to yield either the a type 5-amino-, or the b type 7-amino-1,2,4-triazolo[1,5-a]-pyrimidine derivatives 6–10 was studied. The structure of compounds 6 and 9 was proved by their degradation to the corresponding derivatives 17a and 18a , respectively, through intermediates 11a, 12a, 13a, 14a, 15a and 16a , respectively. The structure of derivatives 7, 8 and 10 was proved on the basis of the analogy of their uv spectra with those of 6a and 9a , respectively. The isolation of the intermediates 19 and 20 helped to prove the mechanism of the reactions leading to the formation of 6a and 9a , respectively. In the reaction of the N-substituted 5-amino-1,2,4-triazoles with 5a the expected condensed ring products were not formed. Instead the aminoacrylates 22 and 24 were obtained. The “Z”-“E” isomeric structure of derivatives 19, 20, 22 and 24 was proved with the help of their pmr spectra. The “Z” isomeric structure of the thermodynamically stabile 22 was corroborated with the help of its proton coupled cmr spectra, too.     

Anil-Synthese. 15. Mitteilung. Über die Herstellung von heterocyclisch substituierten Stilbenyl-Derivaten des 2H-1,2,3-Triazols

Preparation of heterocyclic substituted stilbenyl derivatives of 2H-1,2,3-triazole Schiff's bases derived from 2- and 4-(p-formylphenyl)-2H-1,2,3-triazoles and o- or p-chloroaniline are reacted with various p-tolyl substitued aromatic heterocycles in the presence of dimethylformamide and potassium hydroxide or potassium t-butoxide to yield the corresponding heterocyclic substituted stilbenes (“Anilsynthesis”). In order to avoid opening of the 2H-1,2,3-triazole ring, the reaction is carried out without external heating. In many cases an improvement in yield is obtained by irradiation with UV. light at the beginning of the reaction.     

Carbon-13 NMR investigation of the structure of hydroxy-azoloazines with a bridgehead nitrogen

Carbon-13 nmr data has been obtained on four hydroxy-azoloazines containing a bridgehead nitrogen atom, on the corresponding methoxide derivatives, and on selected anionic and cationic derivatives. These results have been interpreted in terms of the site of protonation of the parent hydroxy-compounds. A comparison of the anionic derivatives with those of the parent compounds demonstrate that the neutral parent hydroxy-species exist predominately in the “hydroxy form” rather than as the ionized species. The chemical shift data also provides information on the conformation of the hydroxy- and methoxy-groups in 8-hydroxy-6-methyl-s-triazolo[4,3-6]-pyridazine and 8-rnethoxy-6-methyl-s-triazolo[4,3-6]pyridazine.     

1,5-naphthyridines. Synthesis of 7-chloro-4-(4-diethylamino-1-methylbutylamino)-2-methoxy-1,5-naphthyridine and related compounds

The synthesis of 7-chloro-4-(4-diethylamino-1-methylbutylamino)-2-methoxy-1,5-naphthyridine, a compound which incorporates the structure of both chloroquine (a schizontocidal drug) and pamaquine (a gametocytocidal drug), has been carried out. In addition, two structurally related derivatives, the, “5-azachloroquine” and the “5-azapamaquine,” have also been obtained by multi-step syntheses. “5-Azachloroquine” possesses good antimalarial activity against Plasmodium berghei. The compound was also found to be less toxic than the known 4-aminoquinoline and 8-aminoquinoline antimalarial drugs.     

Electron-impact induced fragmentation of 2-substituted pyridines and picolines

The fragmentation patterns obtained upon electron impact on 2-nitro-, 2-chloro, and 2-aminopyridines, as well as those of the corresponding 3-, 4-, 5- and 6-picolines were examined. There was considerable departure from those patterns reported for the corresponding benzenoid derivatives. Although the molecular ion from 2-nitro-3-picoline did not show fragment ions attributable to an “ortho-effect” (unlike o-nitrotoluene), those from 2-chloro- and 2-amino-3-picolines did show a loss of HCl and NH₃, respectively. Quite unexpectedly the ions from 2-chloro- and 2-amino-6-picolines also lost HCl and NH₃. Such meta-eliminations for the 2-substituted-6-picolines are postulated to be preceeded by either hydrogen or methyl migration. The mass spectra of 2-pyridone, 2-pyridthione and their respective 3-, 4-, 5- and 6-methyl analogs were also studied. The primary fragmentations of the 2-pyridones were as expected from those reported in the literature. The ions from 3- and 6-methyl-2-pyridones lost water also, the former being another example of an “ortho-effect” observed in this series. Of the thiones, the fragmentations of 3-methyl-2-pyridthione proved most unique since its molecular ion showed besides the loss of HS, the pronounced elimination of H₂S, the latter presumably due to an “ortho-effect.” Figures are presented to illustrate the patterns and metastable ions are indicated when found for the transitions discussed.     

Enzyme-catalyzed synthesis of natural and unnatural polysaccharides

Synthesis of natural and unnatural polysaccharide was achieved via “enzymatic polymerization” by utilizing a glycoside hydrolase as catalyst. Particularly, hyaluronan, chondroitin, and their derivatives belonging to glycosaminoglycans have been prepared using sugar oxazoline monomers designed on the basis of the concept “transition-state analogue substrate”. The oxazoline derivatives of N-acetylhyalobiuronate [GlcAβ(1→3)GlcNAc] and N-acetylchondrosine [GlcAβ(1→3)GalNAc], which have the repeating disaccharide structures of hyaluronan and chondroitin, respectively, were successfully polymerized by the catalysis of hyaluronidase, giving rise to synthetic hyaluronan and chondroitin. Their 2-substituted oxazoline derivatives were also polymerized to the corresponding N-acylated hyaluronan and chondroitin derivatives. Furthermore, N-acetylchondrosine oxazoline derivatives sulfated at the C4, the C6, and both the C4 and C6 of the GalNAc unit were catalyzed by hyaluronidase; the monomer sulfated at the C4 was polymerized to chondroitin 4-sulfate with well-defined structure, whereas the other two monomers were exclusively hydrolyzed to the corresponding disaccharides. These different kinds of natural and unnatural polysaccharides having relatively high molecular weights were produced in all cases by the catalysis of hyaluronidase. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5014–5027, 2006     

Relationships between NMR shifts and interaction energies in biphenyls,alkanes, aza-alkanes,and oxa-alkanes with X─H…H─Y and X─H…Z (X,Y = C or N; Z = N or O) hydrogen bonding

Hydrogen–hydrogen C─H^…H─C bonding between the bay-area hydrogens in biphenyls, and more generally in congested alkanes, very strained polycyclic alkanes, and cis-2-butene, has been investigated by calculation of proton nuclear magnetic resonance (NMR) shifts and atom–atom interaction energies. Computed NMR shifts for all protons in the biphenyl derivatives correlate very well with experimental data, with zero intercept, unit slope, and a root mean square deviation of 0.06 ppm. For some congested alkanes, there is generally good agreement between computed values for a selected conformer and the experimental data, when it is available. In both cases, the shift of a given proton or pair of protons tends to increase with the corresponding interaction energy. Computed NMR shift differences for methylene protons in polycyclic alkanes, where one is involved in a very short contact (“in”) and the other is not (“out”), show a rough correlation with the corresponding C─H^…H─C exchange energies. The “in” and “in,in” isomers of selected aza- and diaza-cycloalkanes, respectively, are X─H^…H─N hydrogen bonded, whereas the “out” and “in,out” isomers display X─H^…N hydrogen bonds (X = C or N). Oxa-alkanes and the “in” isomers of aza–oxa-alkanes are X─H^…O hydrogen bonded. There is a very good general correlation, including both N─H^…H─Y (Y = C or N) and N─H^…Z (Z = N or O) interactions, for NH proton shifts against the exchange energy. For “in” CH protons, the data for the different C─H^…H─Y and C─H^…Z interactions are much more dispersed and the overall shift/exchange energy correlation is less satisfactory.     

Thiamorphinans. I

The present paper deals with the synthesis of 5,5a,6,7,8,9-hexahydro-5,9a-iminoethano-4H-naphtho[2,1-b] -thiophenes (I) as derivatives of the first of three novel isomeric S-heterocycles with morphinan-like structure (“thiamorphinans”).     

Synthesis and biosynthesis of alkoxylipids.

Chromatographic methods have shown that lipids with long alkyl or 1-alkenyl chains–called alkoxylipids or ether lipids–are widely distributed in human and animal tissues. These compounds comprise neutral alkoxylipids, i. e. 1-O-alkyl or 1-O-(1-alkenyl)-2,3-di-O-acylglycerols, and alkoxylipids which are linked by a phosphate residue at C-3 to aminoethanol, choline or serine. 1-O-Alkylglycerols, 1-O-(1-alkenyl)glycerols and other natural alkoxylipids can be synthesized in high yields. 2-Alkyl, 1,3-dialkyl and trialkylglycerols which are not found in nature are also accessible by synthesis. The neutral alkoxylipids are employed in biomedical investigations, e.g. as substrates in acyl-hydrolase systems or in fat absorption studies. The principal features of alkoxylipid biosynthesis have been elucidated. The alkyl residue is derived from a saturated or monounsaturated fatty acid via the corresponding alcohol. 1-O-(1-alkenyl)-2-O-acylglycerophosphoryl aminoethanols (“plasmalogens”) are apparently formed from the appropriate 1-alkyl compounds; this is not possible in the case of the choline series. Both “aminoethanol” and “choline” plasmalogens are, nevertheless, present in most tissues.     

3,6-二氯哒嗪-金鸡纳生物碱衍生物催化不对称“中断的”Feist-Bénary反应的研究

将3,6-二氯哒嗪-金鸡纳生物碱衍生物用于催化β-二羰基化合物与溴乙酰甲酸乙酯/β-取代的溴乙酰甲酸乙酯的不对称“中断的”Feist-Bénary反应, 得到了较高的化学产率(72%～97%)和最高达93% ee的立体选择性.     

Pd(II) -catalyzed addition polymerizations of strained polycyclic olefins

Cationic Pd(II) -complexes with weakly coordinating ligands were used for the olefin addition polymerization of strained polycyclic olefins. The cyclic structure of the monomers remained intact during the reaction which contrasts with products obtained from the olefin metathesis polymerization. The Pd(II) -catalyzed polymerizations showed the features of a “living” polymerization, when norbornene and selected exo-substituted norbornene derivatives were used as the monomers. Endo- and exo-dicyclopentadiene, exo-1,2-dihydrodicyclopentadiene, endo, exo-1,4,5,8-dimethano-1,2,3,4,4a,5,8,8a-octahydronaphthalene and endo, exo-1,4,5,8-dimethano-1,4,4,a,5,8,8a-hexahydronaphthalene were converted into the corresponding rigid polymers. The exo-substituted monomers were found to polymerize at a higher rate than the corresponding or similar endo-substituted monomers. The polymerization of norbornadiene and the subsequent thermal elimination of cyclopentadiene resulted in the formation of polyacetylene.     

The Preorganization Effect of the Calix[4]arene Platform on the Extraction Properties of Acetylhydrazide Groups with Transition Metal Ions

The binding properties of the cone conformer of O,O,O,O-tetrakis[hydrazinocarbonylmethyl]-4-tert-butylcalix[4]arene, the cone and the 1,3-alternate conformers of the corresponding thia analogue have been evaluated by means of liquid–liquid extraction for a large variety of metal ions. The extraction constants and the stoichiometries of the complexes formed have been determined. Comparison of the extraction properties of calix[4]arenes with their acyclic monomeric analogue clearly demonstrated, that the preorganization of acetylhydrazide groups on the calix[4]arene platform is the cause for a significant improvement of its binding properties. The presence of additional “soft” nitrogen binding sites in acetylhydrazide derivatives of calix[4]arenes compared to their amide derivatives leads to a shift from their classical selectivity for alkali and alkaline earth cations to transition metals. The cone conformer of tetrathiacalix[4]arene shows higher selectivity in a series of d-metal ions compared with its “classical” analogue. The 1,3-alternate conformer exhibits an excellent extraction selectivity for Cu²⁺ and Hg²⁺.     

Stereoselective and Convenient Synthesis of Diethyl (E)-α-Triphenylstannyl or (Z)-α-Tributylstannyl α-Alkenylphosphonates

Diethyl (E)-α-triphenylstannyl or (Z)-α-tri-n-butylstannyl α-alkenylphosphonates are conveniently and stereoselectively prepared using a “tin-Peterson-like” reaction. Protonolysis of the carbon-tin bond of α-tributylstannyl derivatives proved to be easy and stereospecific.     

Heterocyclic compounds. VII. Synthesis of thiadiazasteroid analogs

The synthesis of a number of β-northiadiaza steroid analogs has been described. Suitable o-aminonitriles were acylated with γ-chlorobutyryl chloride. These amidonitriles were cyclized to substituted γ-lactams and subsequently to the tetracyclic products. To functionalize the “17-position” in these steroids, the intermediate γ-lactams were converted to arylidene derivatives before cyclization to the tetracyclic derivatives.     

Mass spectra of 6-ketononanolides and related ketolactones

The mass spectral fragmentation of 6-ketononanolides, 6- and 7- ketodecanolides, 7-ketoundecanolides and 9-ketotridecanolide has been partially correlated via high resolution measurements and the use of methyl substituted derivatives. Moities characteristic of the “lactone side” and the “non-lactone side” of the ketolactones can be described. Metastable transitions and decoupled measurements are offered as additional evidence for some of these pathways.     

Yb(OTf)3催化苯乙酮、芳香醛和芳香胺的Mannich反应: 三组分“一锅法”合成β-氨基酮衍生物

报道了稀土化合物Yb(OTf)₃催化的苯乙酮、芳香醛和芳香胺Mannich反应, 三组分“一锅法”合成了一系列的β-氨基酮衍生物. 该方法操作简单、条件温和、产率较高、催化剂可重复使用, 且对环境友好.     

Efficient One Pot Synthesis of Phenylimidazo[1,2-a]pyridine Derivatives using Multifunctional Copper Catalyst Supported on β-Cyclodextrin Functionalized Magnetic Graphene oxide

In this paper, a novel, “green”, efficient and atom-economical methodology for the synthesis of N-(alkyl)-2-phenylimidazo[1,2-a]pyridin-3-amine derivatives based on copper catalyzed oxidative cyclization is presented. An efficient copper nanocatalyst was fabricated by immobilization of Cu on β-Cyclodextrin (βCD) functionalized magnetic graphene oxide nanosheets (denoted as Cu@βCD@MGO). This catalyst primarily oxidizes benzylic alcohols to aldehydes by aerobic O₂. The obtained aldehydes, in situ, takes part in a three component reaction with pyridin-2-amine and isocyanides to produce corresponding N-(alkyl)-2-phenylimidazo[1,2-a]pyridin-3-amine derivatives. The catalyst was characterized by TEM, SEM, VSM, FT-IR, XRD, TGA and ICP. As an advantage, the catalyst showed to be highly recoverable and no appreciable leaching was observed after 10 runs.     

Synthesis of amidocrownophanes with 27‐ and 28‐membered rings and their molecular recognition toward urea and its derivatives

Novel crownophanes with 27‐ and 28‐membered rings having two hydroxyl groups, two amide groups, and aromatic moieties such as naphthalene, pyridine, and phenyl rings were successfully synthesized by a one‐step reaction from the corresponding macrocyclic polyethers via “tandem Claisen rearrengement” in moderate yields. They can solubilize urea and its derivatives into chloroform solution, while the corresponding macrocyclic polyethers do not solubilize them. According to NMR studies, crownophanes 1 and 2 interact with urea and its derivatives forming 1:1 complexes.     

Alkyl Ether Analogs of Chlorophyll-a Derivatives: Part 1. Synthesis, Photophysical Properties and Photodynamic Efficacy

The synthesis, preliminary in vivo biological activity, singlet oxygen and fluorescence yields of a series of alkyl ether derivatives of chlorophyll-a analogs are described. For short-chain carbon ethers (1–7carbon units), it was observed that the biological activity increased by increasing the length of the carbon chain, being maximum in compounds with n-hexyl and n-heptyl chains. Related sensitizers prepared by reacting 2-(1-bromoethyl)-2-devinylpyropheophorbide-a with (sec)alcohols were found to be less effective. Under similar treatment conditions, photosensitizers containing cis- and trans- 3-hexenyl side chains were ineffective. Thus, both stereochemical and steric factors caused differences in sensitizing activity. In general, pyropheophorbide-a analogs were found to be more active than related chlorin e₆ derivatives, in which the isocyclic ring (ring “E”) was cleaved. Related photosensitizers in the 9-deoxy- series were found to be as effective as the corresponding pyropheophorbide-a analogs. The photosensitizers prepared from pyropheophorbide-a methyl ester and chlorin e₆ trimethyl ester have long wavelength absorption at 660 nm (ε 45000 to 50000). Reduction of the carbonyl group in the pyropheophorbide-a to methylene (ring E) resulted in a blue shift to 648 nm (ε 38000).