Synthesis and Reactions of Some New Thieno[2,3-C]pyridazine Derivatives

The alkylation of 4-cyano-5,6-dimethylpyridazin-3(2H)-thione 3 with some halo compounds gave the S-alkylated products 4a–c , which upon treatment with ethanolic sodium ethoxide afforded the cyclized thienopyridazines 5a–c as products. Pyridazothienotriazines 6a–c were prepared by the treatment of compounds 5a–c with nitrous acid, while their reaction with triethyl orthoformate and with carbon disulfide gave the corresponding pyrimidothienopyridazines 7a–c , and 8a–c , respectively. S-alkylated products 9a–o were obtained by the reaction of 8a–c with some halo compounds.     

Thermal [2+3]‐Cycloadditions of trans‐1‐Methyl‐2,3‐diphenylaziridine with CS and CC Dipolarophiles: An Unexpected Course with Dimethyl Dicyanofumarate

The thermal reaction of trans‐1‐methyl‐2,3‐diphenylaziridine (trans‐ 1a ) with aromatic and cycloaliphatic thioketones 2 in boiling toluene yielded the corresponding cis‐2,4‐diphenyl‐1,3‐thiazolidines cis‐ 4 via conrotatory ring opening of trans‐ 1a and a concerted [2+3]‐cycloaddition of the intermediate (E,E)‐configured azomethine ylide 3a (Scheme 1). The analogous reaction of cis‐ 1a with dimethyl acetylenedicarboxylate ( 5 ) gave dimethyl trans‐2,5‐dihydro‐1‐methyl‐2,5‐diphenylpyrrole‐3,4‐dicarboxylate (trans‐ 6 ) in accord with orbital‐symmetry‐controlled reactions (Scheme 2). On the other hand, the reactions of cis‐ 1a and trans‐ 1a with dimethyl dicyanofumarate ( 7a ), as well as that of cis‐ 1a and dimethyl dicyanomaleate ( 7b ), led to mixtures of the same two stereoisomeric dimethyl 3,4‐dicyano‐1‐methyl‐2,5‐diphenylpyrrolidine‐3,4‐dicarboxylates 8a and 8b (Scheme 3). This result has to be explained via a stepwise reaction mechanism, in which the intermediate zwitterions 11a and 11b equilibrate (Scheme 6). In contrast, cis‐1,2,3‐triphenylaziridine (cis‐ 1b ) and 7a gave only one stereoisomeric pyrrolidine‐3,4‐dicarboxylate 10 , with the configuration expected on the basis of orbital‐symmetry control, i.e., via concerted reaction steps (Scheme 10). The configuration of 8a and 10 , as well as that of a derivative of 8b , were established by X‐ray crystallography.     

Dihydroazulene-Azobenzene-Dihydroazulene Triad Photoswitches

Photoswitch triads comprising two dihydroazulene (DHA) units in conjugation with a central trans-azobenzene (AZB) unit were prepared in stepwise protocols starting from meta- and para-disubstituted azobenzenes. The para-connected triad had significantly altered optical properties and lacked the photoactivity of the separate photochromes. In contrast, for the meta-connected triad, all three photochromes could be photoisomerized to generate an isomer with two vinylheptafulvene (VHF) units and a cis-azobenzene unit. Ultrafast spectroscopy of the photoisomerizations revealed a fast DHA-to-VHF photoisomerization and a slower trans-to-cis AZB photoisomerization. This meta triad underwent thermal VHF-to-DHA back-conversion with a similar rate of all VHFs, independent of the identity of the neighboring units, and in parallel thermal cis-to-trans AZB conversion. The experimental observations were supported by computation (excitation spectra and orbital analysis of the transitions).     

The forcing number of toroidal polyhexes

The forcing number, denoted by f(G), of a graph G with a perfect matching is the minimum number of independent edges that completely determine the perfect matching of G. In this paper, we consider the forcing number of a toroidal polyhex H(p,q,t) with a torsion t, a cubic graph embedded on torus with every face being a hexagon. We obtain that f(H(p,q,t)) ≥ min{p,q}, and equality holds for p ≤ q or p > q and t∈{ 0,p−q,p−q + 1,..., p−1}. In general, we show that f(H(p,q,t)) is equal to the side length of a maximum triangle on H(p,q,t). Based on this result, we design a linear algorithm to compute the forcing number of H(p,q,t).     

Haloaldehyde polymeres XIII. Polydibromofluoroacetaldehyde

Dibromofluoracetaldehyde (DBFA) was prepared by reducing methyl dibromofluoroacetate with lithium aluminium hydride (LAH) at low temperatures whereby theLAH was added to dibromofluoroacetate. The initially obtainedDBFA hydrate was dehydrated to the free aldehyde. Methyl dibromofluoroacetate was synthesized together with methyl bromodifluoroacetate by air oxidation of 1,1-dibromo-2,2-difluoroethylene. The mixture of oxidation products, consisting of two acid halides, was treated with methanol and gave a mixture of the methyl esters which here separated by distillation. DBFA was polymerized with anionic and cationic initiators to crystalline insoluble poly-DBFA. Poly-DBFA degraded quantitatively at elevated temperatures to monomericDBFA. Copolymerization ofDBFA with chloral gave copolymers with nearly the same comonomer composition as the feed.DBFA was also copolymerized with phenyl isocyanate to a copolymer which contained acetal and urethane linkages.Part XII:R. W. Campbell, andO. Vogl, Makromolekulare Chemie, in press.     

Synthesis of 4-hydroxy-6,9-difluorobenz[g]isoquinoline-5,10-diones and conversions to 4-hydroxy-6,9-bis[(aminoalkyl)amino]-benz[g]isoquinoline-5,10-diones

Synthetic procedures have been developed which lead to 4-hydroxy-6,9-difluorobenz[g]isoquinoline-5,10-dione ( 4a ) and its 3-methyl analogue 4b . Attempts to displace the fluorides from 4a with N,N-dimethylethylenediamine were unsuccessful. Analogue 4a on treatment with N-(t-butoxycarbonyl)ethylene diamine led to 15 , formed from addition of the nucleophilic amine to C-3. On the other hand, analogue 4b , on treatment with N,N-dimethylethylenediamine led to the anticipated difluoride displacement product 3c . The protection of the hydroxy group of 4a by benzylation with phenyldiazomethane led to 4c which on treatment with N-(t-butoxycarbonyl)ethylene diamine or N,N-dimethylethylenediamine led to the corresponding 6,9-bis-substituted analogues 18a and 18b , respectively. Reductive debenzylations of 18a and 18b by hydrogenation over Pearlman's catalyst also effected partial reductions of the quinone. However, air oxidation of the over reduced products led to 3a and 3b , respectively. Treatment of 3a with hydrogen chloride gas led to the hydrochloride salt of 3d . Addition of O-p-Methoxybenzyl-N,N'-diisopropylurea to 4a led to the p-methoxybenzyl analogue 4d . Treatment of 4d with N,N-dimethylethylene diamine or N-(t-butoxycarbonyl)ethylene diamine led to displacements of the fluorides to yield 18c and 18d , respectively. Deprotection of 18c to 3b was accomplished using methanesulfonic acid. Treatment of 18d with trifluoroacetic acid followed by addition of maleic acid led to dimaleate salt of 3d .     

Rapid and Selective Photo-degradation of Polymers: Design of an Alternating Copolymer with an o-Nitrobenzyl Ether Pendant

The development of polymers with on-demand degradability is required to alleviate the current global issues on polymer-waste pollution. Therefore, we designed a vinyl ether monomer with an o-nitrobenzyl (oNBn) group as a photo-deprotectable pendant (oNBnVE) and synthesized an alternating copolymer with an oNBn-capped acetal backbone via cationic copolymerization with p-tolualdehyde (pMeBzA). The resultant alternating copolymer could be rapidly degraded into lower-molecular-weight compounds upon simple exposure to UV irradiation without any reactants or catalysts, while it was sufficiently stable toward heat and ambient light. This degradation proceeds via cleavage of the hemiacetal structure generated upon photo-deprotection of the oNBn pendant. The oNBn-peculiar degradability allowed the exclusive photo-degradation of the oNBnVE/pMeBzA segments in a diblock copolymer composed of oNBnVE/pMeBzA and benzyl vinyl ether (BnVE)/pMeBzA segments.     

Domino‐Heck Reactions of Carba‐ and Oxabicyclic,Unsaturated Dicarboximides: Synthesis of Aryl‐Substituted,Bridged Perhydroisoindole Derivatives

The C? C coupling of the two bicyclic, unsaturated dicarboximides 5 and 6 with aryl and heteroaryl halides gave, under reductive Heck conditions, the C‐aryl‐N‐phenyl‐substituted oxabicyclic imides 7a – c and 8a – c (Scheme 3). Domino‐Heck C? C coupling reactions of 5, 6 , and 1b with aryl or heteroaryl iodides and phenyl‐ or (trimethylsilyl)acetylene also proved feasible giving 8, 9 , and 10a – c , respectively (Scheme 4). Reduction of 1b with LiAlH₄ (→ 11 ) followed by Heck arylation and reduction of 5 with NaBH₄ (→ 13 ) followed by Heck arylation open a new access to the bridged perhydroisoindole derivatives 12a , b and 14a , b with prospective pharmaceutical activity (Schemes 5 and 6).     

The photo cycloaddition of alkenes to s-triazolo[4,3-b] and [2,3-b]pyridazines

s-Triazolo[4,3-b]pyridazine (I) reacted with cyclohexene under the influence of ultraviolet light to yield 4a,5,7,8,8a,9-hexahydro-9-methylene-6H-s-triazolo[1,5-a]indole (IV) and 9-cyanomethyl-4a,5,7,8,8a,9-hexahydro-6H-s-triazolo[1,5-a]indole (V). These products were formed by the addition of the alkene to the 1,8 positions of I with a concurrent cleavage of the N₄? N₅ bond. Similar additions were observed with cyclopentene and 2,3-dimethyl-1,3-butadiene. The isomeric s-triazolo[2,3-b]pyridazine (III) reacted with cyclohexene to form an isomer of IV, 4a,5,7,8,8a,9-hexahydro-9-methylene-6H-s-triazolo[4,3-a]indole (XV) and two [2 + 2] cycloadducts (XVI and XVII).     

Hetero‐Seeding and Solid Mixture to Obtain New Crystalline Forms

Para‐methyl benzyl alcohol (p‐MeBA II) and para‐chloro benzyl alcohol (p‐ClBA) are quasi‐isostructural and share the same hydrogen‐bond patterns, but their crystals are not isomorphous. No new polymorphs could be obtained by conventional polymorph screening based on different solvents and different crystallization conditions. Formation of a new polymorph of p‐MeBA named p‐MeBA I, isomorphous with the crystal of p‐ClBA, was induced by hetero‐seeding with a small quantity of powdered p‐ClBA added to a supersaturated solution of p‐MeBA in hexane, while seeding of p‐ClBA with p‐MeBA II failed to give a new phase of p‐ClBA isomorphous with known crystalline p‐MeBA II. Mixed crystals of p‐MeBA and p‐ClBA were also prepared with different p‐MeBA/p‐ClBA ratios to understand the role of the different functional groups in the crystal structure. Crystal phases were characterized by combined use of single‐crystal and powder X‐ray diffraction, differential scanning calorimetry, and solid‐state NMR spectroscopy.     

Copolymers of phenylacetylene and para‐nitrophenylacetylene with nonlinear optical properties: Further insight on the conformational structure

Copolymers of phenylacetylene (PA) and para‐nitrophenylacetylene (pNPA), named poly(PA‐co‐pNPA), were obtained in different PA/pNPA ratios and different reaction conditions with Rh(I) catalysts. The structure of the copolymers was investigated with IR, laser Raman, ¹H NMR, electron spin resonance (ESR), and diffuse reflective ultraviolet–visible (DRUV) light spectroscopies. The pristine polymers had a cis–transoidal structure as the predominant conformation with some trans sequences. Detailed ESR studies supported by computer simulation and conformation analysis have suggested that the trans sequences were due to pNPA sequences and that the cis‐C?C bond sequences of pNPA were associated with a stabilized cis radical formed by four to five of pNPA monomers. This particular stabilization was probably the reason for the higher reactivity of pNPA as compared with PA. These cis sequences were preferentially cleaved to generate π radicals. The compression and, to a minor extent, thermal treatment of poly(PA‐co‐pNPA) samples induced a cis‐to‐trans isomerization, leading to a trans–transoidal form with a planar zigzag structure and with a conjugation length up to n = 24 repeat units, determined by DRUV and Raman experiments. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2365–2376, 2004     

One‐pot PTC synthesis of polyfused pyrazoles

Thienopyrazole 2 , 3 , 5 , or 6 and thienopyrazolothiazepine 7, 9 , and 11 derivatives were prepared via the reaction of the 3‐aminopyrazoline‐5‐one 1 with CS₂ and different molar ratio of a variety of halo compounds having an active methylene under PTC conditions. Also, treatment of 1 with CS₂ and alcoholic KOH in 2:1:1 molar ratio afforded dipyrazolopyridine derivatives 12 and 14 . On other hand, the pyrazolothiadiazineone derivative 13 was obtained by treating compound 1 with CS₂ and alcoholic KOH in 1:2:2 molar ratio. Under PTC conditions, compound 1 , CS₂, and ethyl cyanoacetate or malononitrile to gave the pyrazolopyridine derivatives 16 and 17 . Coupling of compound 1 with diazonium acetates afforded the hydrazone derivatives 18a,b , which were oxidized with bromine to give pyrazolotriazoles 19a,b or cyclized with aldehydes to give pyrazolotriazine derivatives 20a–e . Bromination of compound 1 afforded monobromopyrazole derivative 21 , which could be condensed to a dipyrazolopyrazindione 23 . Finally, the dibromopyrazole derivative 22 was cyclized with 2‐mercaptoethanol or o‐phenylenediamine to give the spiropyrazoles 24a,b . © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:211–217, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10129     

Syntheses of 7H-pyrido-and 7H-pyrano[2,3,4-kl]acridin-2(3H)-ones from 9-chloroacridines

A method for peri-annulation of the pyridine or pyran ring to acridine was developed and used to obtain 7H-pyrido-and 7H-pyrano[2,3,4-kl]acridin-2(3H)-ones. The peri-groups were formed by a reaction of 9-chloro-1-nitroacridine with a CH-acid (malononitrile, ethyl cyanoacetate, and ethyl malonate) followed by reduction of the nitro group, or by a reaction of 1-amino-10-methylacridone with PCl₅ and then with a CH-acid. Replacement of the chlorine atom in 9-chloro-1-methoxyacridines by the residue of the CH-acid with subsequent heating in an acidic medium afforded 7H-pyrano[2,3,4-kl]acridin-2(3H)-ones, which belong to a novel heterocyclic system. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1605–1610, September, 2006.     

Benzofuranyl-pyran-2-ones, -pyridazines,and -pyridones from naturally occurring furochromones (visnagin and khellin)

The novel and versatile enaminones 2a,b were synthesized by treatment of visnaginone methyl ether 1a or khellinone methyl ether 1b with N,N-dimethylformamide dimethylacetal. They were reacted with hippuric acid or N-acetylglycine to yield benzofuran-5-yl-2H-pyran-2-ones 3a–d . The reaction of 2a,b with cyanoacetamide and malononitrile dimer in sodium ethoxide gave benzofuran-5-yl-pyridones 4a,b and [benzofuran-5-yl-1H-pyridine-2-ylidene] malononitrile 5a , respectively. Refluxing 2a,b with hydrazine hydrate or with hydroxyla- mine afforded benzofuran-5-yl-1H-pyrazoles 6a,b and benzofuran-5-yl-isoxazoles 7a,b , respectively. Moreover, 2a,b coupled with aryl diazonium salt in the presence of sodium hydroxide to yield 3-(benzofuran-5-yl)-2-aryl-hydrazono-3-oxo-propanals 8a,b which were excellent precursors for the synthesis of pyridazines 9–12 . © 2003 Wiley Periodicals, Inc. 15:85–91, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10219     

Light-Controlled Destruction and Assembly: Switching between Two Differently Composed Cage-Type Complexes

We report on two regioisomeric, diazocine ligands 1 and 2 that can both be photoswitched between the E- and Z-configurations with violet and green light. The self-assembly of the four species ( 1 -Z, 1 -E, 2 -Z, 2 -E) with Co^II ions was investigated upon changing the coordination vectors as a function of the ligand configuration (E vs Z) and regioisomer ( 1 vs 2 ). With 1 -Z, Co₂( 1 -Z)₃ was self-assembled, while a mixture of ill-defined species (oligomers) was observed with 2 -Z. Upon photoswitching with 385 nm to the E configurations, the opposite was observed with 1 -E forming oligomers and 2 -E forming Co₂( 2 -E)₃. Light-controlled dis/assembly was demonstrated in a ligand competition experiment with sub-stoichiometric amounts of Co^II ions; alternating irradiation with violet and green light resulted in the reversible transformation between Co₂( 1 -Z)₃ and Co₂( 2 -E)₃ over multiple cycles without significant fatigue by photoswitching.     

Protein-like copolymers: Computer simulation

The model ofAB copolymers with a “protein-like” primary sequence was developed. This type of copolymers was obtained in a computer experiment. First, the conformation of a collapsed dense homopolymer globule was generated and then, based on this conformation, the primaryAB sequence was determied by denoting the monomeric units located near the surface of the globule as unitsA and those constituting the core of the globule as unitsB. After that, the primary structure of the chain was fixed, and different interaction potentials for theA andB units were introduced. Drawing an analogy of this model to aqueous solutions of globular proteins,A units were interpreted as hydrophilic, andB units were regarded as hydrophobic. By means of Monte Carlo simulation using the bond fluctuation model, the coli—globule transition in “protein-like”AB copolymer, induced by an increase in the attraction between the hydrophobicB units, was studied. The coil—globule transition in a copolymer with the “protein-like” primary sequence occurs at a higher temperature and has higher rate and is sharper than that in a random copolymer with the sameA/B composition and in a random block copolymer with the sameA/B composition and the same “degree of blockiness”. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 884–889, May, 1998.     

Preparation of two triflate precursors for <Emphasis Type="Italic">O</Emphasis>-(2-[<Superscript>18</Superscript>F] fluoroethyl)-<Emphasis Type="Italic">L</Emphasis>-tyrosine used in positron emission tomography (PET)

Two novel triflate precursors for radiolabelling of L-tyrosine in positron emission tomography (PET) for tumor imaging, O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine methyl ester 9a and O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine tert-butyl ester 9b, are synthesized. The triflate agent, 9a or 9b, is prepared by esterification of methanol or transesterification of tert-butyl acetate with L-tyrosine, protection of the amine group with di-tert-butyl dicarbonate, alkylation with chlorohydrin, and triflation with trifluoromethanesulfonic anhydride in four steps with overall yields of 30% and 15%, respectively.     

A complete characterization for <Emphasis Type="Italic">k</Emphasis>-resonant Klein-bottle polyhexes

A hexagonal tessellation K(p, q, t) on Klein bottle, a non-orientable surface with cross-cap number 2, is a finite-sized elemental benzenoid which can be produced from a p × q-parallelogram of hexagonal lattice with usual identifications of sides and with torsion t. Unlike torus, Klein bottle polyhex K(p, q, t) is not transitive except for some degenerated cases. We shall show, however, that K(p, q, t) does not depend on t. Accordingly, criteria for K(p, q, t) to be k-resonant for every positive integer k will be given. Moreover, we shall show that K(3, q, t) of 3-resonance are fully-benzenoid.      

Computational Study of Chronoamperometry at Rectangular Microelectrodes

Three (space) dimensional diffusion to a rectangular microelectrode of length l and width w, embedded in an infinite coplanar insulator is simulated with boundary conditions for a chronoamperometric experiment. An alternating direction implicit finite difference method (Douglas‐Gunn algorithm) utilizing a problem adapted grid is used to solve the diffusion equation. Current transients are computed for different values of the dimensionless length parameter L=l/w, starting with L=1, i.e., a square electrode. Edge effects at the four sides of the rectangular electrode as well as the vertex effect contribute to the total current. With increasing L the transients approach the behavior of a microband electrode transient, where diffusion is essentially two dimensional. The breakdown of the two dimensional diffusion approach with decreasing values of L is analyzed and quantified. This serves as a guideline for analyzing transients measured with electrodes where the condition l » w is not fulfilled.     

Synthesis and polymerization of (E)‐p‐[(p‐methoxyphenyl)‐2‐ethenyl]phenylacetylene with Ziegler–Natta,rhodium, and palladium complexes

The synthesis and polymerization of (E)‐p‐[(p‐methoxyphenyl)‐2‐ethenyl]phenylacetylene was carried out with a homogeneous vanadium acetylacetonate/aluminum triethyl catalyst system, a bis(rhodium chloride cycloocta‐1,5‐diene) complex, and a palladium/trimethylsilyl complex. In all cases, the main fraction was a polymer with a stereoregular structure. The polymerization with the vanadium catalyst gave a polymer fraction in a low yield. The polymerization of (E)‐p‐[(p‐methoxyphenyl)‐2‐ethenyl]phenylacetylene with the soluble rhodium complex gave a polymer in a high yield. The soluble palladium/chlorotrimethylsilane complex gave a polymer in a good yield. On the basis of the spectroscopic data, the poly{(E)‐p‐[(p‐methoxyphenyl)‐2‐ethenyl]phenylacetylene)} obtained, in all cases, showed a cis–transoidal stereoregular structure. The molecular mass of poly{(E)‐p‐[(p‐methoxyphenyl)‐2‐ethenyl]phenylacetylene)} was determined by the matrix‐assisted laser desorption/ionization time‐of‐flight technique. The kinetics of the reaction were analyzed. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 6438–6444, 2005