Zur frage transanularer II-II-wechselwirkungen im [2.2]metacyclophan, [2.2]Paracyclophan und 2,2′-spirobiindan

Concerning the question of transanular II-II-interactions in [2.2]metacyclophane, [2.2]paracyclophane and 2,2′-spirobiindane.From the quotient of the two dissociation constants (K₁/K₂) of [2.2]metacyclophane-bis-chromtricarbonyl (9·0 ± 1·9) it was concluded that there are no transanular II-II-interactions between the two benzene rings. The corresponding values for the bis-chromtricarbonyl-complexes of 2,2′-spirobiindane and [2.2]paracyclophane are 8·0 ± 1·5 and 10⁴, resp. These results are supported by IR-spectroscopical data of the CO-frequencies of the Cr(CO)₃-complexes of [2.2]metacyclophane and some derivatives, of 2,2′-spirobiindane and [2.2]paracyclophane.Moreover, UV-spectroscopic studies of tetracyanoethylene complexes of arenes are shown to be insignificant with regard to transanular II-II-interactions.     

Regioselective intramolecular bridging of p-tert-butylcalix[10]arene

The synthesis and characterization of a series of regioselective intramolecular bridging of calix[10]arene are described for the first time. Reacting p-tert-butylcalix[10]arene with tri-ethylene glycol ditosylate using K₂CO₃ as a base in toluene, 1,2-calix[10]crown-4 2a, 1,4-calix[10]crown-4 2b and 1,6-calix[10]crown-4 2c were obtained in yields of 9%, 14% and 7%, respectively. While using Cs₂CO₃/acetone instead of K₂CO₃/toluene, the 1,4-calix[10]crown-4 2b was obtained selectively in good yield up to 50%.     

Facile Preparation and Molecular Structure of a Novel Metacyclophane

Abstract

A novel 1,1,10,10,19,19-hexamethyl-5,14,23-trimethoxy[3.3.3]metacyclophane (2) was prepared in 25% yield by Friedel–Crafts cyclization of 4-(2-methoxyphenyl)-2-methylbutan-2-ol (1) at ? 78 °C using TiCl₄ as Lewis acid catalyst in anhydrous dichloromethane. The structure of cyclophane 2 was determined by single-crystal X-ray diffraction, and the impact of substrate concentration on the yield of macrocycle 2 was also examined. The study on the effect of substituents at the phenyl ring showed that the methoxy group in 1 is crucial for its trimerization to give the hexamethyl[3.3.3]metacyclophane derivative. Demethylation of 2 with BBr₃ gave 1,1,10,10,19,19-hexamethyl-5,14,23-trihydroxy[3.3.3]metacyclophane (4) in 96% yield, and its three hydroxyl groups provide the possible modification sites for further construction of supramolecular assemblies.     

Chemo-, regio- and stereospecific addition of adenine and 8-azaadenine to α,β-acetylenic γ-hydroxy nitriles: a short-cut to novel acyclic adenosine analogues

Adenine (9H-purin-6-amine) adds readily to available α,β-acetylenic γ-hydroxy nitriles under mild conditions (molar ratio 1:1, K₂CO₃, DMF, rt, 10 min) to afford chemo-, regio- and stereospecifically (Z)-3-(6-amino-9H-purin-9-yl)-4-hydroxy-4-alkyl-2-alkenenitriles, novel functionalized acyclic nucleoside analogues (95-98% yield). Under similar conditions (K₂CO₃, DMF, rt, 1 h), 8-azaadenine (3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-amine) reacts with 4-hydroxy-4-methyl-2-pentynenitrile nonselectively at the 7-, 8- and 9-positions to give the corresponding adducts in a 1:10.5:9 ratio, the total yield being 81%. Chemo-, regio- and stereospecific addition of 8-azaadenine to the above α,β-acetylenic γ-hydroxy nitriles leading to (Z)-3-(7-amino-2H-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-4-hydroxy-4-alkyl-2-alkenenitriles in 44-90% yield is attained when the reaction is carried out without solvent in the presence of Et₃N (30 mol %), the molar ratio of 8-azaadenine:α,β-acetylenic nitriles being 1:2.0 (rt, 12-38 h).     

[2.2. …] Metacyclophane

The synthesis of [2.2.2] metacyclophane (yield 7,5%), [2.2.2.2]metacyclophane (yield 1,7%), [2.2.2.2.2]metacyclophane (yield 5,1%), [2.2.2.2.2.2]metacyclophane (yield 3,1%) and [2.2.2.2.2.2.2.2]metacyclophane (yield 0,5%) by a WURTZ reaction with α,α'-dibromo-m-xylene is described. The structure of the new ring systems was confirmed by UV.-, NMR.- and mass spectra analyses. In connection with the resulting melting points and NMR.-spectra probable conformations of these higher ring systems are discussed.     

Stereoselective sulfur extrusion reaction of syn- and anti-10,20-dibromo-2,3,12,13-tetrathia[4.4]metacyclophanes to the corresponding syn- and anti-dithia[3.3]metacyclophanes

A new cyclophane, 10,20-dibromo-2,3,12,13-tetrathia[4.4]metacyclophane (1) , has been synthesized by the oxidative coupling reaction of 2,6-bis(mercaptomethyl)-1-bromobenzene with I₂. Both syn and anti isomers of 1 can be isolated at room temperature. The thermal sulfur extrusion reaction of anti- 1 with (Et₂N)₃P afforded anti-9,18-dibromo-2,11-dithia[3.3]metacyclophane, while syn- 1 gave 9,19-dibromo-2,11,12-trithia[3.4]metacyclophane. syn-9,18-Dibromo-2,11-dithia[3.3]metacyclophane was produced from the photochemical sulfur extrusion of syn- 1 with (MeO)₃P.     

Synthesis of (Aza)n[3n]cyclophanes as host molecules

(Aza)_n[3ⁿ]cyclophanes were synthesized by the coupling reaction of p-toluenesulfonamide and bis(halomethyl) derivatives in the presence of a base (K₂CO₃, NaH etc.) using DMF, dioxane etc. as a solvent, in acceptable yields. Tetraaza macrocyclic compound (the dimer in Fig. 1) obtained by the coupling of 2,11-diaza[3.3]metacyclophane with 1,3-bis(bromomethyl)benzene gavea 1:1 adduct with benzene.Presented partly at the 42nd Autumn Annual Meeting of the Chemical Society of Japan, Sendai, September, 1980; Abstr. No. 1J17.     

Palladium-Catalyzed Coupling Reaction of Iodouracil Having Acetamidine Moiety with Olefins

The reaction of 6-[1-Aza-2-(dimethylamino)prop-l-enyl]-5-iodo-1,3-dimethyluracil (3) with various olefins in the presence of a catalytic amount of Pd(OAc)₂ and 1.5 equiv. of K₂CO₃ in DMF at 120 °C gave the pyrido[2,3-d]pyrimidine derivatives (5a-b and 7a-d) in moderate to high yield.     

Novel Methods of Synthesis of Dibenzo[3n]crown-n and Their Cation Binding Studied by Fluorescence Spectroscopy. Part V

The dibenzo[3n]crown-n were synthesised starting from bis[2-(o-hydroxyphenoxy)ethyl]ether obtained from bis[2-(o-formylphenoxy)ethyl]ether via Baeyer-Villiger oxidation in H₂O₂/CH₃COOH in a good yield. The cyclic condensation ofbis[2-(o-hydroxyphenoxy)ethyl]etherwith tri- and tetraethylene glycol bisdichlorides andthe bisditosylate of pentaethylene glycol in DMF/Me₂CO₃ afforded the large cyclic ethers of dibenzo[21]crown-7, dibenzo[24]crown-8 and dibenzo[27]crown-9. The structures were analysed with IR, ¹H NMR, ¹³C NMR and low-resolution mass spectroscopy methods. The Na⁺, K⁺, Rb⁺ and Cs⁺ cations' recognition of the molecules were conducted withsteady-state fluorescence spectroscopy. The 1:1 association constants, K_a, in acetonitrile were estimated. Dibenzo[21]crown-7 was the best both for K⁺ and Rb⁺ binding but showed too small an effect on Cs⁺. Dibenzo[24]crown-8 exhibited the binding power in the order of Rb⁺ > K⁺ > Na⁺ > Cs⁺. However, dibenzo[27]crown-9 displayed marked binding with only K⁺ but not with Rb⁺ or with Cs⁺ cations probably due to the heavy atom effect of fluorescence quenching.     

Design and synthesis of novel quinoline derivatives bearing oxadiazole,isoxazoline, triazolothiadiazole,triazolothiadiazine, and piperazine moieties

A new series of 2,3-disubstituted quinoline derivatives were synthesized from 2-chloroquinoline-3-carbaldehyde. In the reaction sequence, acetanilide was cyclized to give 2-chloroquinoline-3-carbaldehyde 1 , which was transformed to 2-(4-phenylpiperazin-1-yl)quinolin-3-carbaldehyde 2 by reaction with 4-phenylpiperazine in DMF-containing anhydrous K₂CO₃; then, compound 2 was oxidized by iodine in methanol, and methyl 2-(4-phenylpiperazin-1-yl)quinoline-3-carboxylate 3 was synthesized. The key intermediate 4 , 4-amino-5-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-4H-1,2,4-triazole-3-thiol, was prepared using the ester 3 by a series of step. Reaction of 5 with various aromatic carboxylic acids or phenacyl bromides yielded 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles 5a-c and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines 6a-c , respectively. Moreover, compound 2 condensed with o-phenylenediamine to give 2-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-1H-benzimidazole 7 . Interaction of 7 and 2-chloromethyl-5-aryl-1,3,4-oxadiazoles in the presence of K₂CO₃ led to the title compounds 8a-c . Furthermore, 4,5-dihydroisoxazoline derivatives 9a-c were obtained by the reaction of readily accessible starting materials including 2-(4-phenylpiperazin-1-yl)quinolin-3-carbaldehyde 2 , 1-phenyl-2-(triphenylphosphoranylidene)ethanone and hydroximoyl chlorides under mild conditions in the presence of Et₃N. The hydrazone intermediates 10a-c were obtained by the condensation of 2 with aroylhydrazides in ethanol, then, refluxing in acetic anhydride yielded 3-acetyl-5-aryl-2-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-2,3-dihydro-1,3,4-oxadiazoles 11a-c . Structures of these compounds were established by their elemental analysis, IR, ¹H NMR, and mass spectral data.     

An Approach to Molecular Baskets with Ester-Crown Handles from Diphenylglycoluril

A series of basket-shaped hosts with ester-crown handles have been synthesized by treating oligoethylene glycol bischloroacetates [ClCH₂CO(OCH₂CH₂) _n OCOCH₂Cl, n = 1, 2, 3, 4] and 1,2-bis(hydroxyethoxy)benzene bischloroacetates with a diphenylglycoluril-based molecular clip, 1,3:4,6-bis(3,6-dihydroxy-1,2-xylylene)tetrahydro-3a,6a-diphenylimidazo[5,5]imidazole-2,5(1H, 3H)-dione (1), in dimethyl sulfoxide using K₂CO₃ as a base in yields of 15, 35, 40, 38, and 20%. Their structures were identified by nuclear magnetic resonance and mass spectrum. The reaction conditions were also studied and optimized. Translated from Journal of Wuhan University (Natural Science Edition), 2005, 51(3) (in Chinese)     

Synthesis and ion selectivity of macrocyclic metacyclophanes analogous to spherand-type calixarenes

Novel macrocyclic compounds, hexahydroxy[1.0.1.0.1.0]- (2b) and octahydroxy[1.0.1.0.1.0.1.0]metacyclophane (2c) have been prepared in 50–70% yield by base-catalyzed condensation of 5,5-di-tert-butyl-2,2-dihydroxybiphenyl (1) with formaldehyde in refluxing xylene. An attempted alkylation of the flexible macrocycles2b and2c with ethyl bromoacetate in the presence of Cs₂CO₃ under acetonitrile reflux gave only one pure stereoisomer3 and4, respectively, while other possible isomers were not observed. The structural characterization of these products is also discussed. The two-phase solvent extraction data indicated that hexaethyl ester3 and octaethyl ester4 show strong metal affinity, comparable with that of the corresponding calix[n]arenes, and a high K⁺ selectivity was observed for octaethyl ester4.¹H-NMR titration of hexaethyl ester3 and octaethyl ester4 with KSCN clearly demonstrate that a 11 complex is formed which is stable on the NMR time scale.This paper is dedicated to the commemorative issue on the 50th anniversary of calixarenes.     

Preparation of substituted 1,2,3,4-tetrahydroquinoxalines and 2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepines from catalytic CpIr hydrogen transfer N-heterocyclization of anilino alcohols

The [Cp^∗IrCl₂]₂/K₂CO₃ catalyzed hydrogen transfer N-heterocyclization on a series of anilino alcohols has been investigated. The catalyst (20% loading) converts anilino alcohols to 1,2,3,4-tetrahydroquinoxalines and 2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepines in 30-84% isolated yield.     

Divergent synthesis of spirocyclopentene-pyrazolones and pyrano[2,3-c]-pyrazoles via Lewis base controlled annulation reactions

An effective Lewis base catalyst-controlled α-regioselective annulation reaction of γ-substituted allenoates with unsaturated pyrazolones has been developed, affording various spirocyclopentene-pyrazolones and pyrano[2,3-c]pyrazoles. The combination of PPh₃ and K₂CO₃ promoted the [3+2] annulation to access the spirocyclopentene-pyrazolones in moderate to good yields (up to 90%) with excellent diastereoselectivities (dr >19:1), while [4+2] annulations to generate pyrano[2,3-c]pyrazoles were successfully achieved by employing DBU as catalyst (in up to 92% yield). Of importance, the asymmetric synthesis of spirocyclopentene-pyrazolone was realized by using our previously reported chiral ferrocenylphosphine catalyst.     

New developments in the Pd-catalysed cyclisation-coupling reaction of alkene-containing carbonucleophiles with organic halides (and triflates). The first examples of asymmetric catalysis.

The results of our preliminary investigations directed toward asymmetric catalysis of the cyclocarbopalladation of alkenes bearing a proximate nucleophile with organic halides (or triflates) are disclosed. A series of bidentate phosphine ligands were evaluated in intramolecular versions of this reaction using (E)-2-[7-(2-bromophenyl)-hept-4-enyl]-malonic acid dimethyl ester (1) and (Z)-2-[7-(2-trifluoromethanesulfonyloxy-phenyl)-hept-4-enyl]-malonic acid dimethyl ester (9) as model substrates. The highest enantioselective induction was obtained with aryl triflate 9 which produced the corresponding cyclopentylindane as a single diastereomer in 54% chemical yield and 43% ee by using PdCl₂[S-(−)-TolBINAP] as chiral catalyst and K₂CO₃ as base.     

Photochemical Ring Enlargement of Macrocyclic N‐Phenyl Imides into Cyclophanes

Allylic N‐phenyl imides containing 12‐ and 14‐membered rings, such as compounds 3 and 12 , are easily synthesized by ring enlargement from cycloalkanones and phenyl isocyanates. Irradiation of 3 and 12 in EtOH and MeCN, with high‐ and low‐pressure Hg lamps, led, via the photo‐Fries rearrangement, to the same primary products: the orthocyclophane 8 and the paracyclophane 9 from 3 (Scheme 2), and the corresponding compounds 13 and 14 from 12 (Scheme 3). Besides the primary photorearrangement products, secondary products, the aminocyclophanes 10 and 11 , or 15 and 16 , respectively, were also formed. The total yields of the four products were very high when the N‐phenyl imides were irradiated in MeCN with a low‐pressure Hg lamp: 97 and 93%, respectively. If the para‐position in 3 or 12 is blocked by a Me group, the para‐photo‐Fries rearrangement is prevented. In this case, only one primary photoproduct is formed: the corresponding orthocyclophane ( 17 or 23 , resp.). The most remarkable result was observed on irradiation of the 12‐membered N‐(4‐tolyl) imide 5 in MeCN (low‐pressure lamp). It reacted nearly quantitatively to give only two products: 15‐methyl‐1‐aza[12]orthocyclophane‐2,12‐dione (=16‐methyl‐2‐azabicyclo[12.4.0]octadeca‐1(14),15,17‐triene‐3,13‐dione; 17 ) in 80% yield and 17‐amino‐14‐methyl[11]metacyclophane‐1,11‐dione (=17‐amino‐15‐methylbicyclo[11.3.1]heptadeca‐1(17),13,15‐triene‐2,12‐dione; 19 ) in 16% yield (Scheme 5).     

Facial one-pot synthesis of D3h symmetric bicyclocalix[2]arene[2]triazines and their layered comb self-assembly

A number of D_3h symmetric bicyclocalix[2]arene[2]triazine core compounds were synthesized via a general and good-yielding (43–48% yield) facile protocol starting from cyanuric halides, phloroglucinol and K₂CO₃ under very mild reaction conditions. These cage-like compounds are tolerante with different reaction conditions and can be derived with other functional groups in high yields. The X-ray crystal structures show these compounds have slightly distorted D_3h symmetric structures. Due to the unique molecular topological structure, bicyclocalix[2]arene[2]triazine molecules form unique layered comb networks when hydrogen bond groups exist (such as CO₂H, B(OH)₂), which represent a new kind of building block unit for supramolecular architectures.     

Potassium Carboxylates by Direct Carbonylation of Potassium Alkoxides

Reaction of the K⁺ alkoxide of linalool ( 1 ) in benzene with CO at 425–440 bar and 120–130° for 12–30 h gave the K⁺ salt of 2,6-dimethyl-2-vinyl-5-heptenoic acid ( 4a ) in a ca. 25% yield based on ca. 65% converted alkoxide. Reaction of the [K⁺ ? 18-crown-6] alkoxide of 1 with CO at 50–55 bar and 40° for 90–140 h gave a mixture containing mainly the [K⁺ ? 18-c-6] salts of 4a (ca. 62%) and of the homogeranic acids 3a and 6a (together ca. 27% of the mixture) in a ca. 35% combined yield based on 50–60% converted alkoxide. The uncomplexed or complexed K⁺ alkoxide of (S)? 1 gave, with ca. 85% net retention, the K⁺ salt of (S)- 4a . Reaction of the [K⁺ ? 18-c-6] alkoxide of geraniol ( 2 ) with CO at 50 bar and 40° for 65–70 h gave myrcene ( 10 ) and geranyl formate ( 11 ) in a ca. 40–50% yield each based on ca. 85% converted alkoxide. Reaction of the [K⁺ ? 18-c-6] alkoxide of 3-pentyl-1,4-pentadien-3-ol ( 14 ) at 50 bar and r.t. for 70 h gave a mixture of the [K⁺ ? 18-c-6] salts of 2-pentyl-2-vinyl-3-butenoic acid ( 15a ) (67%) and the 4-pentyl-2,4-hexadienoic acids 18a and 19a (together 23% of the mixture) in a ca. 90% combined yield based on ca. 65% converted alkoxide.     

Generation of diazo-2-methylenecyclopropane and its 1,3-dipolar cycloaddition to acrylates

N-(2-Methylenecyclopropyl)-N-nitrosourea (2) was synthesized for the first time (yield 70%) and its decomposition induced by bases was studied. In particular, treatment with MeONa/MeOH at-30°C in the presence of methyl methacrylate gives the corresponding I-pyrazoline stereoisomers, the products of [3+2]-cycloaddition of diazo-2-methylene-cyclopropane (1) generatedin situ. Decomposition of2 on treatment with K₂CO₃ at 0–5°C in the presence of acrylonitrile also proceeds as [3+2]-cycloaddition: however, the expected 2-pyrazoline easily isomerizes into 5(3)-isopropenyl-3(5)-cyanopyrazole. Buta1,2,3-triene is the main product of base-induced decomosition of2 in the absence of unsaturated substrates. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1210–1214, July, 2000.     

Photoactive cryptands. Synthesis of the sodium cryptates of macrobicyclic ligands containing bipyridine and phenoanthroline groups

The NaBr cryptates of five macrobicyclic ligands containing bipyridine (bpy) and phenanthroline (phen) groups, i.e, of [bpy.bpy.bpy] 1 [bpy.bpy.phen] 2 [phen.phen.-phen] 3 [2.1.phen] 4 and [2.2.phen] 5 , have been prepared. 1, 2, 4 and 5 have been obtained in high yield by condensation of bis(bromomethyl)bipyridine 6 or -phenanthroline 9 with the corresponding macrocyclic diamines in presence of Na₂CO₃. Direct access to the NaBr complexes of th symmetrical cryptands 1 and 3 was achieved by a one-step macrobicyclisation procedure. The metal-ion complexes of ligands 1-5 have the attractive feature of combining the cation inclusion, nature of cryptates with the photoactivity of bipyridine and phenanthroline groups; they may thus be expected to posses a variety of interesting physical and chemical properties.