A novel reaction of (2a7-trinito-9H-fluoren-9-ylidene)-propanedinitrile with N-arylisoindolines

N-Arylisoindolines 1a-c reacted with (2,4, 7-trinitro-9H-fluoren-9-ylidene)propanedinitrile ( A ) in pyridine with admission of air via a net α-H-atom abstraction and formation of [3-(2-aryl-3-arylimino-2,3-dihydro- 1H-isoindol-1-ylidene)-2-aryl-2,3-dihydro-1H-isoindol-1-ylidene]propanedinitriles 2a-c , N-[2-aryl-3-(2-aryl-3-arylimino-2,3-dihydro-1H-isoindolyl-1-idene)-2,3-dihydro-1H-isoindol-1-ylidene]arenamines 3a, b , N, N'-[2-aryl-1H-isoindole-1,3(2H)-diylidene]bisarenamines 4a, b and N-arylphthalimides 5a-c in moderate yields. 2,4,7-Trinitro-9-fluorenone as well as one reduction product each of the latter and of A, namely compounds 6 and 7 , respectively, are also found. The structure of 2b has been unambiguously confirmed by an X-ray crystal structure analysis. A rationale for the conversions observed is presented. These involve dehydrogenation and oxidative couplings of 1a-c as well as transfer of N-aryl fragment from 1a-c to intermediate products.     

Synthesis of 3-(2-chloro-5-nitroanilino and 4-nitroanilino)-1-(2,4,6-trichlorophenyl)-2-pyrazolin-5-ones

A new synthesis of 3-anilino-1-aryl-2-pyrazolin-5-ones in which the pyrazolinone ring is built via N? N bond formation is described. 2-Cyano-2′,4′,6′-trichloroacetanilide 1 was converted to imino ether hydrochloride 2 which was reacted with anilines in methanol to produce N-arylimino ether 3a,b. Reaction of these N-arylimino ethers with hydroxylamine gave N-arylamidoximes 4a,b . An 1,2,4-oxadiazol-5-one 6a was prepared from the N-arylamidoxime 4a and subjected to base-induced rearrangement. The desired 3-anilino-pyrazolinone 7a was obtained only in a very low yield. However, O-acetylation of the N-arylamidoximes 4a,b followed by acid-catalyzed ring closure and rearrangement in the presence of excess acetic anhydride gave a mixture of N-acetylanilinopyrazolinones (e.g. 10 ) and 4-acetyloxy-3-N-acetylanilinopyrazoles (e.g. 12 ) which upon acid hydrolysis afforded the 3-anilinopyrazolinones 7a,b in better yield.     

Cyclisation of 7-Deazaxanthine-9-propionic Acid to an Active-Site-Directed,Irreversibly Acting Inhibitor of Xanthine Oxidase

Phase-transfer alkylation of 2,4-dimethoxy-7H-pyrrolo[2,3-d]pyrimidine ( 2 ) with ethyl 3-bromopropionate leads regioselectively to ethyl 2,3-dimethoxy-7H-pyrrolo[2,3-d]pyrimidine-7-propionate ( 3a ). After saponification and ether cleavage, the functionalised 7-deazaxanthine 4b was obtained. Reaction of 4b with H₂O-soluble carbodiimide resulted in an intramolecular acylation at N(3) with formation of the tricyclic compound 5 . Compound 5 - bearing a reactive lactam ring - is an active-site-directed, irreversibly acting inhibitor of xanthine oxidase from cow's milk.     

C(6)N(7)-cyclized purines

By reaction of 6-[N-(2-hydroxyethyl)-N-methyl]aminopurine ( 2a ) and of the corresponding 3-hydroxypropyl derivative 2b with thionyl chloride a bridge to N(1) is formed yielding 5 and 6 , respectively, whereas from 6-[N-(4-hydroxybutyl)-N-methyl]aminopurine ( 2c ) the 4-chlorobutyl compound 4 is obtained, which cyclizes in alkaline medium to the C(6)-N(7) bridged compound 7 . A related cyclization to 11a–11f is observed when 6-chloropurines are reacted with 3-alkyl-1,3-oxazolidines or 3-methyl-1,3-thiazolidine.     

Reactions of 2-hydroxybenzonitrile with isocyanates

Triethylamine catalyzes the reaction of 2-hydroxybenzonitrile ( 1 ) with aryl isocyanates to form the corresponding carbamates 2a-c , as well as the cyclization of the latter compounds to either 4[N-(N-arylcarbamoyl)-imino]-3-aryl-2H-1,3-benzoxazin-2-ones 4a-c , or 4-arylamino-2H-1,3-benzoxazin-2-ones 7a-c , depending on the reaction temperature. Under analogous conditions, the carbamates obtained from 1 and 2-chloroethyl isocyanate, 3-chloropropyl isocyanate and ethyl isocyanatoacetate undergo a double cyclization yielding imidazo- and pyrimido[1,2-c|1,3]benzoxazinones 13a,b,17 . Upon heating in phenyl ether, compounds 7a-c , rearrange to 2-(2-hydroxyphenyl)-4(3H)-quinazolinones 10a-c .     

Synthesis of 2′-Deoxyribofuranosides of 8-Aza-7-deazaguanine and Related Pyrazolo[3,4-d]pyrimidines

The N(1)- and N(2)-(2′-deoxyribofuranosides) 1 and 2 , respectively, of 8-aza-7-deazaguanine were prepared via phase-transfer glycosylation in the presence or absence of Bu₄NHSO₄ as catalyst of 6-amino-4-methoxy-lH-pyrazolo[3,4-d]pyrimidine ( 7c ) with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D -erythro-pentofuranosyl chloride ( 10 ). On a similar route, but without catalyst and employing THF as organic phase, the 6-amino-4-chloronucleosides 11b and 12b were synthesized from 7a and converted into the N(1)-and N(2)-substituted 4-thioxo analogues 17a and 18a , respectively. The ratio of N(1)- to N(2)-glycosylation was 2:1 for 7c and 1:1 for 7a , viz. depending on the nucleobase structure. The rate of the H⁺-catalyzed N-glycosyl hydrolysis was strongly decreased for the N(2)-(β-D -2′-deoxyribofuranosides) as compared to the N(1)-compounds. However, the N(1)-nucleoside 1 , which is an isostere of 2′-deoxyguanosine, is sufficiently stable to be employed later in solid-phase oligonucleotide synthesis.     

Potential DNA bis-intercalating agents. Bridged bis-(6-chloropurines) and related compounds

Two bis-(6-chloropurines) bridged by conformationally restricted tethers were synthesized as potential DNA bis-intercalating agents. Reduction of 4,6-dichloro-5-nitropyrimidine ( 1 ) afforded 5-amino-4,6-dichloropyrimidine ( 2 ) which was then used as the starting material. Reaction of 2 with 4,4′-diaminodiphenylmethane ( 3 ) and bis-(4-aminophenyl) ether ( 4 ) yielded bis-[4-(N-5-amino-4-chloro-6-pyrimidyl)aminophenyl]methane ( 5 ) and bis-[4-(N-5-amino-4-chloro-6-pyrimidyl)aminophenyl] ether ( 6 ), respectively. Acid-catalyzed condensation of the above pyrimidines, 5 and 6 , with triethyl orthoformate in N,N-dimethylacetamide gave bis-[4-(6-chloro-9-purinyl)phenyl]methane ( 7 ) and bis-[4-(6-chloro-9-purinyl)phenyl] ether ( 8 ). The spectral data on the new compounds will be discussed.     

Network Motifs and Thermal Properties of Copper(I) Halide and Pseudohalide Coordination Polymers with 1, 7‐ and 4, 7‐Phenanthroline

The coordination polymers [CuBr(1, 7‐phen‐κN7)] ( 1a ), [CuI(1, 7‐phen)] ( 2a ) and [(CuI)₂(1, 7‐phen‐κN7)] ( 2b ) may be prepared by treatment of the appropriate copper(I) halide with 1, 7‐phenanthroline (1, 7‐phen) in acetonitrile. 1a exhibits staircase CuBr double chains, 2a novel quadruple CuI chains. Their thermal properties were investigated by DTA‐TG and temperature resolved powder X‐ray diffraction. On heating, both 1:1 compounds decompose to 2:1 polymers and then finally to CuBr or CuI. With 4, 7‐phenanthroline (4, 7‐phen), CuBr affords both 1:1 and 2:1 complexes ( 5a , 5b ), CuI 1:1 , 2:1 and 3:1 complexes( 6a , 6b , 6c ) in acetonitrile at 20 °C. 5a and 6a display lamellar coordination networks, with the former containing zigzag CuBr single chains, the latter 4‐membered (CuI)₂ rings. A second 2:1 complex [(CuI)₂(4, 7‐phen‐μ‐N4, N7)] ( 6b ′) with staircase CuI double chains can be obtained by reacting CuI with 4, 7‐phen in a sealed glass tube at 110 °C. Both 5a and 6a exhibit thermal decomposition pathways of the general type 1:1 → 2:1 → 3:1 → CuX, and novel CuX triple chains are proposed for the isostructural 3:1 polymers 5c and 6c . X‐ray structures are reported for complexes 1a , 2b , [(CuCN)₃(CH₃CN)(1, 7‐phen‐μ‐N1, N7)] ( 3c· CH₃CN), [CuSCN(1, 7‐phen‐κN7)] ( 4a ), 5a , 6a and [CuCN(4, 7‐phen‐μ‐N4, N7)] ( 7a ).     

Total Synthesis of (±)-3-Deoxy-7,8-dihydromorphine, (±)-4-Methoxy-N-methylmorphinan-6-one and 2,4-Dioxygenated (±)-Congeners

A total synthesis of racemic 3-deoxy-7,8-dihydromorphine ((±)- 2 ) and 4-me-thoxy-ALmethylmorphinan-6-one ((±)- 3 ) is described. The key intermediate was 2,4-dihydroxy-N-formylmorphinan-6-one (11) , obtained from 3,5-dibenzyloxy-phenylacetic acid (4) in 41.8% overall yield. Bromination of 11 , and treatment with aqueous N_aOH-solution afforded, after N-deblocking and reductive N-methylation with concomitant removal of the aromatic bounded Br-atom, the morphinanone 14. Elimination of the HO–C(2) group in 14 was accomplished by hydrogenolysis of its N-phenyltetrazolyl ether 15 , to give 3-deoxy-6,0-didehydro-7,8-dihydromorphine (16). Reduction of 16 with L-Selectride at low temperature provided (±)- 2 in high yield. The ether 15 directly afforded, under more vigorous reduction conditions, 4-hydroxy-N-methylmorphinan-6-one (17). and after O-methylation of 17 , the methyl ether (±)- 3 was obtained. A (1:l)-mixture of 4-hydroxy-2-methoxy-N-methylmor-phinan-6-one (28) and its 2-hydroxy-4-methoxy isomer 30 svere obtained by Grewe-cyclization of a mono-methoxylated aromatic precursor similar to that which afforded 11. The 2,4-dioxygenated N-methylmorphinan-6-ones 29 , 31 and 38 were also prepared and characterized.     

Organic Diodes Based on Redox-Polymer Bilayer-Film-Modified Electrodes

The synthesis of four electropolymerizable 2,2′-bipyridinium salts with tuned reduction potential (E₁^°) is described (N,N′-ethylene-4-methyl-4′-vinyl-2,2′-bipyridinium dibromide ( 4 ; E₁^° ?–0.48 V), 4-methyl-N, N′-(trimethylene)-4′-vinyl-2,2′-bipyridinium dibromide ( 5 ; E₁^°? ?0.66 V), N,N′-ethylene-4-methyl-4′-[2-(1H-pyrrol-1-yl)ethyl]-2, 2′-bipyridinium bis(hexafluorophosphate) ( 6b ; E₁^°? ?0.46 V), and 4-methyl-4′-[2-(1H-pyrrol-1-yl)ethyl]-N, N′-(trimethylene)-2,2′-bipyridinium bis(hexafluorophosphate) ( 7b ; E₁^°? ?0.66 V)). E₁^°-Tuning is based on the torsional angle C(3)–C(2)–C(2′)–C(3′), imposed by the N,N′-ethylene and N,N′-(trimethylene) bridge. The vinylic compounds 4 and 5 undergo cathodic, the pyrrole derivatives 6b and 7b anodic electropolymerization on glassy carbon electrodes from MeCN solutions, yielding thin, surface-confined films with surface concentrations of redox-active material in the range 5 · 10^?9 < Γ < 2.10^?8 mol/cm², depending on experimental conditions. The modified electrodes exhibit reversible ‘diquat’ electrochemistry in pure solvent/electrolyte. Copolymerization of 6b or 7b with pyrrole yields most stable electrodes. Bi ayer-film-modified electrodes were prepared by sequential electropolymerization of the monomers. The assembly electrode/poly- 6b /poly- 7b behaves as a switch, it transforms – as a Schmitt trigger – an analog input signal (the electrode potential) into a digital output signal (redox state of the outer polymer film). Forward-(electrode/poly- 7b /poly- 6b ) and reverse-biased assemblies (electrode/poly- 6b /poly- 7b ) were coupled to the electrochemical reduction of redox-active solution species, e.g. N- (cyanomethyl)-N′-methyl-4,4′-bipyridinium bis(hexafluorophosphate) ( 8 ). Zener-diode-like behavior was observed. Aspects of redox-polymer multilayer-film assemblies, sandwiched between two electronic conductors, are discussed in terms of molecular electronic devices.     

Etude dans la série des pyrrolidinones. IV. Formation de quelques dérivés de l'acide L méthylène bis N-(oxo-5 pyrrolidine carboxylique-2)

Starting from the readily available 5-oxo-2-carboxypyrrolidine, methylene-bis-(N-5-oxo-2-carboxypyrrolidine) was prepared and transformed into a diamine, then into two isomeric diols, which cyclised into one ether. The meso configuration has been assigned for this ether. The reduction of both diols and ether was complete and gave rise to methylene-bis-N-pyrrolidine.     

Preparation and Structure of Melemium Melem Perchlorate HC6N7(NH2)3ClO4·C6N7(NH2)3

A new perchlorate salt of melem (2,6,10‐triamino‐s‐heptazine, C₆N₇(NH₂)₃) was obtained from an aqueous solution of HClO₄ at lower concentration than the ones reported for the synthesis of melemium perchlorate monohydrate (HC₆N₇(NH₂)₃)ClO₄·H₂O. The new salt was identified as melemium melem perchlorate (HC₆N₇(NH₂)₃)ClO₄·C₆N₇(NH₂)₃ representing a melem adduct of water free melemium perchlorate. The crystal structure was solved by single‐crystal X‐ray methods ( , no. 2, Z = 2, a = 892.1(2), b = 992.7(2), c = 1201.5(2) pm, α = 112.30(3), β = 96.96(3), γ = 95.38(3)°, V = 965.8(4)·10⁶ pm³, 4340 data, 387 parameters, R1 = 0.039). Melemium melem perchlorate crystallizes in a layer‐like structure containing both protonated HC₆N₇(NH₂)₃ and non protonated C₆N₇(NH₂)₃ moieties in the coplanar layers as well as perchlorate ions between them, all of which being interconnected by hydrogen bonds. Vibrational spectroscopic investigations (FTIR and Raman) of the salt were conducted.     

Synthesis and properties of conformationally locked 1,3-bisalkyl-7-deazaxanthine 2′-deoxy-d-ribofuranosides

1,3-Dimethyl-7-deazaxanthine 2′-deoxyribofuranosides 1a and 6a and their N-3 isopropyl congeners 1b and 6b have been prepared employing the nucleobase anions 7a or 7b and 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythropentofuranosyl chloride ( 8 ) upon glycosylation. The reaction was not stereoselective as found in case of other pyrrolo[2,3-d]pyrimidine nucleosides induced by the bulky N-3 substituent. Configuration of anomers was established by ¹H-nmr nOe difference spectroscopy. Those data also indicated that the conformation around the N-glycosylic bond was locked by the bulky N-3 substituent. Contrary to the purine nucleoside such as wyosine ( 2a ) the hydrolytic stability of the N-glycosylic bond of the pyrrolo[2,3-d]pyrimidine nucleosides was increased by N-3 alkylation. Moreover, it was shown by ¹⁵N-nmr spectroscopy that different to purine nucleosides the aglycon was not protonated in acidic medium. As a result the N-glycosylic bond hydrolysis did not follow an A-1 but an A-2 mechanism.     

7-Substituted 7-Deaza-2′-deoxyguanosines: Regioselective Halogenation of Pyrrolo[2,3-d]pyrimidine Nucleosides

The synthesis of 7-chloro-, 7-bromo-, and 7-iodo-substituted 7-deaza-2′-deoxyguanosine derivatives 2b – d is described. The regioselective 7-halogenation with N-halogenosuccinimides was accomplished using 7-[2-deoxy-3,5-O-di(2-methylpropanoyl)-β-D -erythro- pentofuranosyl]-2-(formylamino)-4-methoxy-7H-pyrrolo[2,3-d]- pyrimidine ( 4 ) as the common precursor. A one-pot reaction (2N aq. NaOH) of the halogenated intermediates 5a – c furnished the desired compounds. Also the 7-hexynyl derivative 2e of 7-deaza-2′-deoxyguanosine is described.     

Neutral counterparts of the C2H7O+ isomers

The neutral counterparts of the C₂H₇O⁺ isomers CH₃O⁺ (H)CH₃, CH₃CH₂OH₂⁺ and $ {\rm C}_2 \,{\rm H}_4 \,\, \cdot \cdot \cdot \mathop {\rm H}\limits^ + \, \cdot \cdot \cdot {\rm OH}_2 $ were studied by neutralization-reionization mass spectrometry. Protonated dimethyl ether and its —O(D)⁺ analogue were produced by protonation (deuteration) of dimethyl ether and also generated as a fragment ion from (labeled) ionized CH₃OCH₂CH(OH)CH₃ by loss of CH₃CO?. It was observed that the dissociation characteristics of the ions and the stability of their neutral counterpart depended on the internal energy of the protonated ether ions. Stable neutral CH₃?(H)CH₃ was only produced from energy-rich ions. The classical protonated ethanol ion CH₃CH₂OH₂⁺ (a) was produced at threshold by the loss of CH₃CO?. from ionized butane-2,3-diol. Mixtures of a with the non-classical ion $ {\rm C}_2 \,{\rm H}_4 \,\, \cdot \cdot \cdot \mathop {\rm H}\limits^ + \, \cdot \cdot \cdot {\rm OH}_2 $ (b) were produced by reaction of C₂H₅⁺ ions with H₂O. As for the protonated ether, only high-energy a and/or b ions yielded stable hypervalent radicals. It is suggested that the stable C₂H₇?O radicals are Rydberg states.     

Reaction of 6-chloro-2-[1-methyl-2-(N-methylthiocarbamoyl)]-hydrazinoquinoxaline 4-oxide with dimethyl acetylenedicarboxylate

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 4a with methyl or phenyl isothiocyanate gave 6-chloro-2-[1-methyl-2-(N-methylthiocarbamoyl)hydrazino]quinoxaline 4-oxide 7a or 6-chloro-2-[1-methyl-2-(N-phenylthiocarbamoyl)hydrazino]quinoxaline 4-oxide 7b , respectively, whose reaction with dimethyl acetylenedicarboxylate afforded 6-chloro-2-[N-methyl-N-(5-methoxycarbonylmethylene-3-methyl-4-oxo-2-thioxoimidazolidin-1-yl)]aminoquinoxaline 4-oxide 8a or 6-chloro-2-[N-methyl-N-(5-methoxycarbonylmethylene-4-oxo-3-phenyl-2-thioxoimidazolidin-1-yl)]aminoquinoxaline 4-oxide 8b , respectively.     

Benzofuran systems. Regioselective bromination and some other reactions of 1-(3-benzofuranyl)-2-phenylethanones

1-[3-(2-Alkylbenzofuranyl)]-2-(3,5-dibromo-4-hydroxyphenyl)ethanones 5a,b and 1-[3-(2-alkylbenzofuranyl)-2-(3-bromo-4-methoxyphenyl)ethanones 3a,b were readily prepared by selective bromination of hydroxy 1a,b and methoxy 1c,d ethanones, respectively. A successful method of O-alkylamination of 5a with N-(2-chloroethyl)-N,N-diethylammonium chloride to 6a by a two-phase reaction under phase transfer conditions has been applied. Lithium aluminium hydride reduction of the carbonyl group of 1b to carbinol 4b was carried out in good yields.     

Polyetherimides. I. Preparation of dianhydrides containing aromatic ether groups

A general synthetic method and characterization of bis(ether anhydride)s, the ether containing aromatic dianhydrides of the following structure, are presented. The method involves aromatic nitro-displacement of N-substituted 3- or 4-nitrophthalimide with bisphenoxides to form N-substituted arylene-bis(phthalimido)ethers or bis(ether imide)s. Sixteen structurally different bis(ether imide)s have been prepared and subsequently converted to the corresponding bis(ether anhydride)s. Bis(ether anhydride)s are stable crystalline compounds of a moderate reactivity. Unlike highly reactive dianydrides such as pyromellitic and benzophenonetetracarboxylic dianhydrides bis(ether anhydride)s are semipermanently stable against hydrolysis in the presence of atmospheric moisture.     

Fused s-triazino heterocycles. XV. 13H-4,6,7,13a,13c-pentaazabenzo[hi]chrysene, 13H-4,7,13a,13c-tetraazabenzo[hi]chrysene,and 7H-3,7,10,10b-tetraazacyclohepta[de]naphthalene,three new ring systems

The reaction of N-cyano-N′-(6-amino-2-pyridyl)acetamidine ( 5a ) and homophthalic anhydride followed by ring closure of the 2-[2-(carboxymethyl)phenyl]-5-methyl-1,3,4,6,9b-pentaazaphenalene intermediate ( 4a ) gave 5-methyl-13-oxo-13H-4,6,7,13a,13c-pentaazabenzo[hi]chrysene ( 8a ). An analogous series starting with 3-N-(6-amino-2-pyridyl)amino-2-cyano-2-butenenitrile ( 5b ) in place of 5a gave in two steps 5-methyl-13-oxo-13-H-4,7,13a,13c-tetraazabenzo[hi]chrysene-6-carbonitrile ( 8b ). Elemental analysis, ir and pmr spectra of 8a , 8b and several new model compounds aided in confirming the structures of 8a and 8b. The synthesis of one of these model compounds for 5b and phenylacetic anhydride led surprisingly to 2-methyl-9-phenyl-7H-3,7,-10,10b-tetraazacyclohepta[de]naphthalene ( 10 ) in addition to the expected 2-benzyl-4-cyano-5-methyl-1,3,-6,9b-tetraazaphenalene ( 7b ).