Synthesis and characterization of novel optically active poly(amide-imide)s via direct amidation

N,N′-Pyromelliticdiimido-di-l-methionine (3) was prepared from the reaction of pyromellitic dianhydride (1) with l-methionine (2) in glacial acetic acid and pyridine solution at refluxing temperature. The direct polycondensation reaction of the monomer diimide-diacid (3) with 1,3-phenylenediamine (4a), 1,4-phenylenediamine (4b), 2,6-diaminopyridine (4c), 3,5-diaminopyridine (4d), 4,4′-diaminodiphenylether (4e) and 4,4′-diaminodiphenylsulfone (4f) was carried out in a medium consisting of triphenyl phosphate, N-methyl-2-pyrolidone, pyridine and calcium chloride. The resulting poly(amide-imide)s having inherent viscosities 0.45-0.53 dl g⁻¹ were obtained in high yields and are optically active and thermally stable. All of the above compounds were fully characterized by IR spectroscopy, elemental analyses and specific rotation. Some structural characterization and physical properties of these new optically active poly(amide-imide)s are reported.     

Reaction between glutaric anhydride and N-benzylidenebenzylamine, and further transformations to new substituted piperidin-2-ones

The reaction between glutaric anhydride (1) and N-benzylidenebenzylamine (3) was studied in detail by ¹H NMR spectroscopy under different reaction conditions. The major product was (±)-trans-1-benzyl-6-oxo-2-phenylpiperidine-3-carboxylic acid (2), which was converted into new substituted piperidin-2-ones via transformations of the carboxylic group. The final products are expected to possess pharmaceutical activities, and the relevant screenings are in course.     

N-Arylmethyl-7-azabicyclo[2.2.1]heptane derivatives: synthesis and reaction mechanisms

N-Arylmethyl-7-azabicyclo[2.2.1]heptane (I) derivatives have been synthesized by deprotection of N-protected, N-(arylmethyl)cyclohex-3-enamines, bromination of the resulting secondary cyclohex-3-enamines, followed by base-promoted cyclization (route a), or by bromination of N-protected, N-(arylmethyl)cyclohex-3-enamines followed by deprotection and base-mediated cyclization (route b). In these protocols we have observed that the bromination of the key intermediates (12, 13, and 19) is stereoselective leading to major trans-3-cis-4-dibromides (14, 17, and 20), whose mild base-mediated heterocyclization (on compound 14), or the two-step acid hydrolysis plus base-promoted cyclization (on compounds 17 and 20), gave products 6 and 7 in good yield. A mechanistic investigation using DFT has been carried out to explain the results observed in this work.     

An improved synthesis of ethyl cis-5-iodo-trans-2-methylcyclohexanecarboxylate, a potent attractant for the Mediterranean fruit fly

Both racemic ethyl 5-iodo-2-methylcyclohexanecarboxylate (1), known as Mediterranean fruit fly attractant ceralure B₁, and its (−)-(1R,2R,5R) enantiomer 1a were conveniently synthesized from commercially available racemic trans-6-methyl-3-cyclohexenecarboxylic acid 2 or its (1R,6R) enantiomer 2a. Key steps included an asymmetric Diels-Alder reaction using a sultam auxiliary and cyclization of the unwanted trans-5-iodo-trans-2-methylcyclohexanecarboxylic acid (8) to the intermediate lactone 7 (or 8a to 7a). The new method may circumvent chromatographic separations and seems amenable to scale-up.     

Studies on the Lossen-type rearrangement of N-(3-phenylpropionyloxy) phthalimide and N-tosyloxy derivatives with several nucleophiles

The reaction of N-(3-phenylpropionyloxy)phthalimide (1a) and N-tosyloxy (5a,b) derivatives with nucleophiles was examined and found to give the products via Lossen-type rearrangement. In order to obtain the scope of this reaction mechanism, further studies the reaction of several N-sulfonyloxyimide derivatives with various nucleophiles under similar conditions were carried out and found to afford the corresponding same types of products in high yields.     

Microwave-promoted synthesis of new optically active poly(ester-imide)s derived from N,N-(pyromellitoyl)-bis-l-leucine diacid chloride and aromatic diols

Pyromellitic dianhydride (benzene-1,2,4,5-tetracarboxylic dianhydride) (1) was reacted with l-leucine (2) in a mixture of acetic acid and pyridine (3:2) and the resulting imide-acid [N,N^′-(pyromellitoyl)-bis-l-leucine diacid] (4) was obtained in quantitative yield. The compound (4) was converted to the N,N^′-(pyromellitoyl)-bis-l-leucine diacid chloride (5) by reaction with thionyl chloride. A new facile and rapid polycondensation reaction of this diacid chloride (5) with several aromatic diols such as phenol phthalein (6a), bisphenol-A (6b), 4,4^′-hydroquinone (6c), 1,8-dihydroxyanthraquinone (6d), 1,5-dihydroxy naphthalene (6e), 4,4-dihydroxy biphenyl (6f), and 2,4-dihydroxyacetophenone (6g) was developed by using a domestic microwave oven in the presence of a small amount of a polar organic medium such as o-cresol. The polymerization reactions proceeded rapidly and are completed within 10 min, producing a series of optically active poly(ester-imide)s (PEIs) with good yield and moderate inherent viscosity of 0.10-0.27 dl/g. All of the above polymers were fully characterized by IR, elemental analyses and specific rotation. Some structural characterization and physical properties of these optically active PEIs are reported.     

Optically active imidazoles derived from enantiomerically pure trans-1,2-diaminocyclohexane

A new exploration of monoprotected derivatives of trans-1,2-diaminocyclohexane as a platform for the synthesis of enantiomerically pure imidazole derivatives is described. The primary amino group (-NH₂), present in the mono-imine derivative of salicylic aldehyde (hemi-salen derivative) 5 was used for sequential reactions with formaldehyde and the corresponding α-(hydroxyimino)ketone. (S)-(−)-1-Phenylethylamine was also used as starting material for the preparation of new imidazole N-oxides 7c and 10a-c, bearing a chiral N-(1-phenylethyl)carboxamido function at C(4). Imidazole N-oxides 10a,b possessing either a Me or i-Pr group at N(1), respectively, follow the known sulfur-transfer pathway to afford the corresponding imidazole-2-thiones 13a,b. However, in the case of imidazole N-oxide 10c with a bulky adamantan-1-yl substituent at N(1), the attempted ‘sulfur-transfer reaction’ led to the deoxygenated imidazole derivative 14. Finally, the same reaction with 7c, which bears an electron-withdrawing N-(1-phenylethyl)carboxamide residue at C(4) of the imidazole ring, yielded a mixture of deoxygenated imidazole 16 and imidazole-2-thione 15c.     

Stereochemical studies—XIII: Cyclic aminoalcohols and related compounds—VI synthesis of the four 2-amino-4-t-butylcyclopentanol isomers

From diethyl 3-t-butyladipate (5), via cis- and trans-4-t-butylcyclopentene-1,2-oxide (31, 32) as key compounds, the syntheses of cis-2-amino-cis-4-t-butylcyclopentanol (1), cis-2-amino-trans-4-t-butylcyclopentanol (2), trans-2-amino-cis-4-t-butylcyclopentanol (3) and trans-2-amino-trans-4-t-butylcyclopentanol (4) have been achieved. 1, 3 and 4 were also synthesized from the corresponding 2-hydroxy-4-t-butylcarboxylic acids by Curtius degradation of the hydrazides (11, 18, 19). The steric course of process leading to the above compounds is discussed.     

Synthesis of a solvent-sensitive highly fluorescent derivative of perfluorocyclopentene

A solvent-sensitive highly fluorescent compound, N-[2-(1′,3′,4′,4′,5′,5′-hexafluorocyclopentenyl)]-4-(5-methoxy-thiazolyl)pyridine (1D) was synthesized as an unexpected product of the reaction of 4-bromo-5-methoxy-2-(4-pyridyl)thiazole (1B) with perfluorocyclopentene in the presence of n-BuLi. Primary mechanism of this reaction was proposed, and the photophysical properties of 1D in different solvents were studied.     

Alkaline hydrolysis of N-bromoiminothianthrene derivatives

5-(N-Bromo)iminothianthrene (2) and 5-(N-bromo)iminothianthrene 10-oxide (5) and 10,10-dioxide (8) were prepared and their alkaline hydrolyses were studied. The compound 2 and cis-5-(N-bromo)iminothianthrene 10-oxide (cis-5) afforded the corresponding sulfoximine exclusively. While, unexpectedly, both trans-5-(N-bromo)iminothianthrene 10-oxide (trans-5) and 8 afforded mainly de-brominated products, trans-5-iminothianthrene 10-oxide (trans-4) and 5-iminothianthrene 10,10-dioxide (7), respectively. In these cases, 5-iminothianthrene 5,10-dioxide (6) (Z- and E-mixture) and 5-iminothianthrene 5,10,10-trioxide (9) and further de-iminated products were also formed respectively as minor products. The stereochemical considerations on the S_N reactions are described in view of the steric effect and ‘flip-flap’ motion of the thianthrene framework.     

Enantioselective synthesis of (1S,2S)-1,2-di-tert-butyl and (1R,2R)-1,2-di-(1-adamantyl)ethylenediamines

An enantioselective synthesis of sterically congested 1,2-di-tert-butyl and 1,2-di-(1-adamantyl)ethylenediamines has been developed. Thus, diastereomerically pure trans-1-apocamphanecarbonyl-4,5-dimethoxy-2-imidazolidinones 6 and 7 were successfully prepared by optical resolution of (±)-trans-4,5-dimethoxy-2-imidazolidinone using apocamphanecarbonyl chloride (MAC-Cl) followed by stereospecific and stepwise substitution of the dimethoxyl groups using tert-butyl or 1-adamantyl cuprates to provide (4S,5S)-4,5-di-tert-butyl and (4R,5R)-4,5-di-(1-adamantyl)-2-imidazolidinones 12 and 15, respectively. Furthermore, N-acetyl 4,5-di-tert-butyl and 4,5-di-(1-adamantyl)-2-imidazolidinones 16a,b were enantioselectively deacetylated using a catalytic oxazaborolidine system to provide enantiopure 1-p-tolylsulfonyl-4,5-di-tert-butyl-2-imidazolidinones 12 and 19 and 1-p-tolylsulfonyl-4,5-di-(1-adamantyl)-2-imidazolidinones 18 and 20, respectively. Finally, N-p-tolylsulfonyl-2-imidazolidinones 12 and 15 were treated with 30 equiv of Ba(OH)₂·8H₂O to achieve ring cleavage and to provide (1S,2S)-1,2-di-tert-butylethylenediamine 3 and (1R,2R)-1,2-di-(1-adamantyl)ethylenediamine 4.     

Aminobis(phenolate)s of imidomolybdenum(VI) and -tungsten(VI)

The reactions of trans-[MoO(ONO^Me)Cl₂] 1 (ONO^Me = methylamino-N,N-bis(2-methylene-4,6-dimethylphenolate) dianion) and trans-[MoO(ONO^tBu)Cl₂] 2 (ONO^tBu = methylamino-N,N-bis(2-methylene-4-methyl-6-tert-butylphenolate) dianion) with PhNCO afforded new imido molybdenum complexes trans-[Mo(NPh)(ONO^Me)Cl₂] 3 and trans-[Mo(NPh)(ONO^tBu)Cl₂] 4, respectively. As analogous oxotungsten starting materials did not show similar reactivity, corresponding imido tungsten complexes were prepared by the reaction between [W(NPh)Cl₄] with aminobis(phenol)s. These reactions yielded cis- and trans-isomers of dichloro complexes [W(NPh)(ONO^Me)Cl₂] 5 and [W(NPh)(ONO^tBu)Cl₂] 6, respectively. The molecular structures of 4, cis-6 and trans-6 were verified by X-ray crystallography. Organosubstituted imido tungsten(VI) complex cis-[W(NPh)(ONO^tBu)Me₂] 7 was prepared by the transmetallation reaction of 6 (either cis or trans isomer) with methyl magnesium iodide.     

Asymmetric Michael addition using N-cinnamoyl- and N-crotonyl-trans-hexahydrobenzoxazolidin-2-ones

Preparation of N-cinnamoyl- and N-crotonyl-oxazolidin-2-ones 2 and 3 or ent-2 and ent-3 from (4S,5S)- and (4R,5R)-trans-hexahydrobenzoxazolidin-2-ones 1 or ent-1 are reported. Stereoselective copper promoted conjugated additions of Grignard reagents to chiral N-enoyl amides 2 and 3 or ent-2 and ent-3 in the presence of Zn(II) salts afforded the 1,4-addition products 4-11 and the corresponding enantiomers.     

trans-Spanning ferrocene amidodiphosphine ligand: Synthesis, palladium complexes and catalytic use in Suzuki-Miyaura cross-coupling

Amide coupling between [2-(diphenylphosphino)phenyl]methylamine and 1′-(diphenylphosphino)ferrocene-1-carboxylic acid (Hdpf) afforded a novel diphosphine-amide, 1-{N-[(2-(diphenylphosphino)phenyl)methyl]carbamoyl}-1′-(diphenylphosphino)ferrocene (1), which was subsequently studied as a ligand for palladium(II) complexes. Depending on the metal precursor, the following complexes were isolated: [PdCl₂(1-κ²P,P′)] (2), [PdCl(Me)(1-κ²P,P′)] (3), [(μ-1){PdCl₂(PBu₃)}₂] (4) and [(μ-1){PdCl(L^NC)}₂] (L^NC = 2-[(dimethylamino-κN)methyl]phenyl-κC¹), featuring this ligand either as a trans-chelating or as a P,P′-bridging donor. The crystal structure of 2·1.25CH₂Cl₂ was established by X-ray crystallography, corroborating that 1 coordinates as a trans-spanning diphosphine without any significant distortion to the coordination sphere. Complex 2 together with a catalyst prepared in situ from 1 and palladium(II) acetate were tested in Suzuki-Miyaura reaction of aryl bromides with phenylboronic acid in dioxane.     

Solvent-free reactions of N,N′-thiocarbonyldiimidazole with ferrocenylcarbinols

The efficient and simple routes for the synthesis of various ferrocenyl derivatives from ferrocenylcarbinols and N,N′-thiocarbonyldiimidazole (TCDI) are described. It involves grinding the two substrates in a Pyrex tube with a glass rod at room temperature. The reaction of ferrocenylmethanol (1a) provided S,S-bis(ferrocenylmethyl)dithiocarbonate (1b), whose crystal structure and a plausible mechanism for its formation are also reported. The reaction of 1-ferrocenyl-1-phenylmethanol (2a) and 1-ferrocenylbutanol (2b) gave the products 2c and 2d, respectively. The reaction of ω-ferrocenyl alcohols 4-ferrocenylphenol (3a) and 6-ferrocenylhexan-1-ol (3b) yielded the products 3c and 3d, respectively. Reaction of 1,1′-ferrocenedimethanol (3e) afforded 3f in moderate yield, and by contrast, it was not similar to 1b. Reaction of [4-(trifluoromethyl)phenyl]methanol (4a) provided the thiocarbonate 4b in good yield.     

Novel optically active poly(amide-imide)s from N,N-(4,4-carbonyldiphthaloyl)-bis-l-phenylalanine diacid chloride and aromatic diamines by microwave irradiation

3,3^′,4,4^′-benzophenonetetracarboxylic dianhydride (4,4^′-carbonyldiphthalic anhydride) (1) was reacted with l-phenylalanine (2) in a mixture of acetic acid and pyridine (3:2) and the resulting imide-acid [N,N^′-(4,4^′-carbonyldiphthaloyl)-bis-l-phenylalanine diacid] (4) was obtained in high yield. The compound (4) was converted to the N,N^′-(4,4^′-carbonyldiphthaloyl)-bis-l-phenylalanine diacid chloride (5) by reaction with thionyl chloride. A new facile and rapid polycondensation reaction of this diacid chloride (5) with several aromatic diamines such as 4,4^′-diaminodiphenyl methane (6a), 2,4-diaminotoluene (6b), 4,4^′-sulfonyldianiline (6c), p-phenylenediamine (6d), 4,4^′-diaminodiphenylether (6e), m-phenylenediamine (6f), benzidine (6g) and 2,6-diaminopyridine (6h) was developed by using a domestic microwave oven in the presence of a small amount of a polar organic medium such as o-cresol. The polymerization reactions proceeded rapidly, compared with the conventional solution polycondensation, and was completed within 7 min, producing a series of optically active poly(amide-imide)s with high yield and inherent viscosity of 0.22-0.52 dl/g. All of the above polymers were fully characterized by IR, elemental analyses and specific rotation. Some structural characterization and physical properties of this optically active poly(amide-imide)s are reported.     

Syntheses and structures of iron carbonyl complexes derived from N-(5-methyl-2-thienylmethylidene)-2-thiolethylamine and N-(6-methyl-2-pyridylmethylidene)-2-thiolethylamine

The reaction of N-(5-methyl-2-thienylmethylidene)-2-thiolethylamine (1) with Fe₂(CO)₉ in refluxing acetonitrile yielded di-(μ₃-thia)nonacarbonyltriiron (2), μ-[N-(5-methyl-2-thienylmethyl)-η¹:η¹(N);η¹:η¹(S)-2-thiolatoethylamido]hexacarbonyldiiron (3), and N-(5-methyl-2-thienylmethylidene)amine (4). If the reaction was carried out at 45 °C, di-μ-[N-(5-methyl-2-thienylmethylidene)-η¹(N);η¹(S)-2-thiolethylamino]-μ-carbonyl-tetracarbonyldiiron (5) and trace amount of 4 were obtained. Stirring 5 in refluxing acetonitrile led to the thermal decomposition of 5, and ligand 1 was recovered quantitatively. However, in the presence of excess amount of Fe₂(CO)₉ in refluxing acetonitrile, complex 5 was converted into 2-4. On the other hand, the reaction of N-(6-methyl-2-pyridylmethylidene)-2-thiolethylamine (6) with Fe₂(CO)₉ in refluxing acetonitrile produced 2, μ-[N-(6-methyl-2-pyridylmethyl)-η¹ (N_py);η¹:η¹(N); η¹:η¹(S)-2-thiolatoethylamido]pentacarbonyldiiron (7), and μ-[N-(6-methyl-2-pyridylmethylidene)-η²(C,N);η¹:η¹(S)-2- thiolethylamino]hexacarbonyldiiron (8). Reactions of both complex 7 and 8 with NOBF₄ gave μ-[(6-methyl-2-pyridylmethyl)-η¹(N_py);η¹:η¹(N);η¹:η¹(S)-2-thiolatoethylamido](acetonitrile)tricarbonylnitrosyldiiron (9). These reaction products were well characterized spectrally. The molecular structures of complexes 3, 7-9 have been determined by means of X-ray diffraction. Intramolecular 1,5-hydrogen shift from the thiol to the methine carbon was observed in complexes 3, 7, and 9.     

Reactivity of 2,3-bis(2-pyridyl)pyrazine with [Re2(CO)8(CH3CN)2]: Molecular structures of [Re2(CO)8(C14H10N4)] and [Re2(CO)8(C14H10N4)Re2(CO)8]

The reaction of the labile compound [Re₂(CO)₈(CH₃CN)₂] with 2,3-bis(2-pyridyl)pyrazine in dichloromethane solution at reflux temperature afforded the structural dirhenium isomers [Re₂(CO)₈(C₁₄H₁₀N₄)] (1 and 2), and the complex [Re₂(CO)₈(C₁₄H₁₀N₄)Re₂(CO)₈] (3). In 1, the ligand is σ,σ′-N,N′-coordinated to a Re(CO)₃ fragment through pyridine and pyrazine to form a five-membered chelate ring. A seven-membered ring is obtained for isomer 2 by N-coordination of the 2-pyridyl groups while the pyrazine ring remains uncoordinated. For 2, isomers 2a and 2b are found in a dynamic equilibrium ratio [2a]/[2b]  =  7 in solution, detected by ¹H NMR (−50 °C, CD₃COCD₃), coalescence being observed above room temperature. The ligand in 3 behaves as an 8e-donor bridge bonding two Re(CO)₃ fragments through two (σ,σ′-N,N′) interactions. When the reaction was carried out in refluxing tetrahydrofuran, complex [Re₂(CO)₆(C₁₄H₁₀N₄)₂] (4) was obtained in addition to compounds 1-3. The dinuclear rhenium derivative 4 contains two units of the organic ligand σ,σ′-N,N′-coordinated in a chelate form to each rhenium core. The X-ray crystal structures for 1 and 3 are reported.     

Novel synthesis of 2,4-bis(2-pyridyl)-5-(pyridyl)imidazoles and formation of N-(3-(pyridyl)imidazo[1,5-a]pyridine)picolinamidines: nitrogen-rich ligands

Heating a neat 1:2 mixture of 2-picolylamine and 2-cyanopyridine followed by treatment of the resultant red gummy substance with aqueous KOH resulted in the isolation of 2,4,5-tris(2-pyridyl)imidazole (1a) as the major product and N-(3-(2-pyridyl)imidazo[1,5-a]pyridine)picolinamidine (2a) in small amounts. Similarly, by using 3-picolylamine, 2,4,-bis(2-pyridyl)-5-(3-pyridyl)imidazole (1b) and N-(3-(3-pyridyl)imidazo[1,5-a]pyridine)picolinamidine (2b) were isolated, and by using 4-picolylamine, 2,4,-bis(2-pyridyl)-5-(4-pyridyl)imidazole (1c) and N-(3-(4-pyridyl)imidazo[1,5-a]pyridine)picolinamidine (2c) were isolated. The plausible mechanism of the formation of 1a-c and 2a-c is delineated.     

Palladium complexes of N-aryl-2-pyridylamines

Palladium complexes of N-phenyl-2-pyridylamine (4) and dipyridylamine substrates (7, 11) have been studied. Due to the coordination ability of the pyridine-nitrogen atoms, the pyridyl substrates, 4, 7, 11 were subjected to Pd(OAc)₂ complexations and a number of N-aryl-2-pyridylamine Pd complexes (13-17) were isolated and characterised, in particular by NMR and ESI-MS. A new method for the preparation of the acetato-bridged six-membered ring palladacycle complex (13) of 4 is reported. The dipyridyl amines 7, 11 formed cis/trans bis-dentate acetato-bridged dimeric Pd₂Lig₂(OAc)₂ (14a,b/16a,b) and Pd₃Lig₂(OAc)₄ complexes (15a,b/17a,b). The N-aryl-2-pyridylamine substrates (4, 7, 11) were prepared by oxidative nucleophilic substitution, by 1,3-cycloaddition reaction or by Buchwald amination.