New polydentate macrocyclic ligands of hybrid amine-imine and amide-imine types as artificial anion receptors. Synthesis and study of anion binding

Three new macrocyclic Schiff bases containing an amine or amide structural fragment along with imine groups were synthesized by condensation of 2,6-bis(2-aminophenyliminomethyl)pyridine (1) and N, N’-bis(2-aminophenyl)pyridine-2,6-dicarboxamide (2) with 2,5-diformylpyrrole (₃) and 2,2-bis(5-formylpyrrol-2-yl)propane (4). The reaction of compound 1 with 3 proceeds abnormally and is accompanied by redox disproportionation of compound 1 in the first step. The structure of the macrocyclic product of this reaction was established by X-ray diffraction analysis. Spectrophotometric titration showed that hybrid macrocycle 10, which was prepared by condensation of compound 2 with 4, possesses the properties of an anion receptor and selectively binds hydrosulfate and dihydrophosphate anions in the presence of bromide and nitrate anions. The structures of 10 and its adduct with the hydrosulfate anion were calculated by density functional theory.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 161–168, January, 2005.     

The synthesis and characterization of copper(II)–<Emphasis Type="Italic">p</Emphasis>-aminosalicylate complexes with diamine ligands

The complexes were synthesized by the reaction between sodium salt of p-aminosalicylic acid (PAS) and Cu(II) for 1 and corresponding ethylenediamine (en) or its derivatives for 2–6. The complexes were characterized by using elemental analyses, FT-IR, UV–Vis, magnetic moment measurements, and thermal analyses techniques. In complex 1[Cu₂(PA)₄(H₂O)₂], two Cu(II) ions were found as bridged by four μ-O:O′ p-aminosalicylato (PA) ligands, forming a cage structure, and two aqua ligands to form dinuclear square-pyramidal geometry around Cu(II) ions. In the complexes 2–6, the PA (anionic form of p-aminosalicylic acid) coordinated to Cu(II) ions as monodentate manner by using its oxygen atom of deprotonated carboxylic acid and ethylenediamine derivatives coordinated to the Cu(II) ions in bidentate manner to form mononuclear octahedral complexes [Cu(PA)₂(L)₂] (L = ethylendiamine, N,N-dimethylethylendiamine, N,N′-dimethylethylendiamine, N,N,N′,N′-tetramethylethylendiamine, and 1,3-propanediamine, for complexes 2, 3, 4, 5, and 6, respectively). In all the complexes OH and NH₂ groups of PA ligands were not coordinated to metals.     

New method for the synthesis of β-tropolones: Structures of condensation products of o-quinones with 2-methylquinolines and the mechanism of their formation

A new method was developed for the synthesis of functionalized β-tropolones based on acid-catalyzed condensation of 2-methylquinoline derivatives with 3,5-di(tert-butyl)-1,2-benzoquinone and 4,6-di(tert-butyl)-3-nitro-1,2-benzoquinone (14). The mechanism of the multistep reaction giving rise to β-tropolones and their tautomerism were studied by quantum chemical methods (DFT B3LYP/6-31G**). The reaction of 2-methylquinoline derivatives containing the tertiary amino group at position 4 with quinone 14 is accompanied by the formation of derivatives of a new heterocyclic system, viz., 4,6-dioxo-2-azabicyclo[3.3.0]octa-2,7-diene N-oxide. The molecular and crystal structures of two 5,7-di(tert-butyl)-3-hydroxy-2-(quinolin-2-yl)tropolones and two dioxoazabicyclooctadiene N-oxides, as well as of the preparatively isolated intermediate of the first condensation step and of the by-product of the reaction were established by X-ray diffraction. Dedicated to Academician O. M. Nefedov on the occasion of his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1956–1977, November, 2006.     

Synthesis and bactericidal activities of novel pyrazole-1-carbothioamide derivatives

4-(2-Hydroxy-phenyl)-but-3-en-2-one (1) was prepared via condensation of salicylaldehyde with acetone, and then reaction of the ketone 1 with thiosemicarbazide was accompanied by cyclization to give substituted pyrazole (2). Seven new 5-(2-hydroxy-phenyl)-3-methyl-4,5-dihydropyrazole-1-carbothioamide derivatives (3a–3g) were synthesized by the acylation of 2 and characterized by means of elemental analysis, infrared (IR), and ¹H nuclear magnetic resonance (NMR). The compounds 3c, 3d, and 3g showed certain bactericidal activity against E. coli; while compound 3g showed certain bactericidal activity against P. vulgaris. Translated from Chinese Journal of Applied Chemistry, 2006, 23(12): 1355–1358 [译自: 应用化学]     

Reaction of cross-conjugated dienones with phenyl-and 2-pyridylhydrazines

New pyrazoline derivatives were synthesized by condensation of dienones based on cyclohexanone and N-substituted piperidin-4-ones with phenylhydrazine and 2-pyridylhydrazine. The reaction with phenylhydrazine produces trans isomers. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2509–2512, November, 2005.     

3,3,3-Trifluoro-<Emphasis Type="Italic">N</Emphasis>′-(3-trifluoromethylphenyl)-1,2-propanediamine and its <Emphasis Type="Italic">N</Emphasis>-mono-and <Emphasis Type="Italic">N,N</Emphasis>-dicarboxyethyl derivatives: synthesis,protolytic and complexation properties

3,3,3-Trifluoro-N′-(3-trifluoromethylphenyl)-1,2-propanediamine (5) was synthesized by the reaction of 2-diazo-1,1,1-trifluoro-3-nitropropane or 3,3,3-trifluoro-1-nitropropene with 3-aminobenzotrifluoride followed by the reduction of the nitro group. The Michael 1,4-addition of diamine 5 to acrylic acid occurs only at the N(1) atom and affords N-mono-or N,N-dicarboxyethyl derivatives 6 and 7, depending on the reactant ratio. Protolytic equilibria 5–7 in aqueous solutions were studied by pH-potentiometry and UV spectroscopy. Only the aliphatic amino group can be protonated in an aqueous solution, while the aromatic amino group remains unprotonated even in 12 M HCl. The stability constants of transition metal (Cu²⁺, Ni²⁺, Zn²⁺) complexes with ligands 5–7 were determined by pH-potentiometric titration. The stability of the complexes and selectivity of the ligands toward Cu²⁺ ions increase with an increase in the number of N-carboxyethyl groups. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2465–2469, November, 2005.     

Synthesis of Derivatives of ω-Isocyanato-α-methylamino, ω-Ureido-α-methylamino, and Nα-Methyl-α, ω-diamino Acids

 Homochiral N^α-methyl-2,3-diaminopropionic and N^α-methyl-2,4-diaminobutyric acid derivatives 8a,b were obtained via a stereoconservative four-step synthesis starting from hexafluoroacetone protected L-aspartic and L-glutamic acid 2a,b, respectively. Hexafluoroacetone protected ω-isocyanato-α-methylamino acids 4a,b– the key intermediates of the synthesis – are versatile building blocks for amino acid and peptide modification and promising candidates for combinatorial chemistry. Upon reaction with alcohols, compounds 4 give activated N ^ω-urethane protected ω-amino-α-methylamino acid derivatives 5–7; upon reaction with amines, ω-ureido-α-methylamino acid derivatives 10–12 and 3-methylamino-pyrrolidin-2-ones 13 are available.     

Synthesis,characterization, and antimicrobial activity of new benzoylthiourea ligands

In this study, new benzoylthiourea derivatives, (E)-N-[(2-benzamidomethyleneamino)ethylcarbamothioyl]benzamide H₃L′, N-(1-(3-benzoylthioureido)propan-2-ylcarbamothioyl)-benzamide H₄L″, (E)-N-[4-(benzamidomethyleneamino)phenylcarbamothioyl]benzamide H₃L‴, were synthesized. Structures of the compounds were identified by spectroscopic techniques. In addition, all synthesized compounds were evaluated for in vitro antibacterial and antifungal activity. Compound H₃L‴ exhibited antibacterial activity.     

SYNTHESIS OF 2,4-DISUBSTITUTED NORTROPINONE DERIVATIVES BY ALDOL CONDENSATION

2,4-Disubstituted nortropinone derivatives 2, with anticipated anticonvulsant activity, were synthesized by the reaction of N-substituted nortropinones, ethanol, 5N-NaOH, and aromatic aldehydes (R₁CHO).     

Diaminomethylidene derivatives of β-oxo sulfones as potential reagents in heterocyclic synthesis and chelating ligands

Active methylene β-oxo sulfones add to the C≡N bond of benzoylcyanamide in the presence of catalytic amounts of Ni(acac)₂. Debenzoylation of the reaction products under the action of MeONa in MeOH gives N,N′-unsubstituted diaminomethylidene derivatives of β-oxo sulfones (acyl(R-sulfonyl)ketene aminals), which can be used as reagents for heterocyclic synthesis and as chelating ligands. The syntheses of 2-amino-3-arylsulfonylpyridin-4(1H)-ones and 5-sulfonylcytosine derivatives are presented as examples.     

Reaction of thiosemicarbazide with n-cyanoguanidine: synthesis of 3,5-diamino-1-thiocarbamoyl-and 3,5-diamino-1-thiazol-2-yl-1,2,4-triazoles

The reaction of thiosemicarbazide with N-cyanoguanidine in an acidic medium afforded 3,5-diamino-1-thiocarbamoyl-1,2,4-triazole, whose condensation with α-halo ketones gave 3,5-diamino-1-thiazol-2-yl-1,2,4-triazoles 7a–d. The latter were also prepared by the independent synthesis from 2-hydrazinothiazoles and N-cyanoguanidine. Acylation of compounds 7a,d under mild conditions and their condensation with aldehydes occur at the C(3′)NH₂group. The structure of aroyl derivative 11c was established by X-ray diffraction. Acylation of diaminothiazolyltriazole 7a in boiling Ac₂O afforded 3,5-diacetylamino-1-(4-phenylthiazol-2-yl)-1,2,4-triazole. Hydrogenation of arylidene derivatives 14b,c and aroyl derivative 11c gave the corresponding benzylaminotriazoles 15a,b. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 329–334, February, 2006.     

Synthesis of Derivatives of ω-Isocyanato-α-methylamino, ω-Ureido-α-methylamino,and N<Superscript>α</Superscript>-Methyl-α, ω-diamino Acids

Summary.  Homochiral N^α-methyl-2,3-diaminopropionic and N^α-methyl-2,4-diaminobutyric acid derivatives 8a,b were obtained via a stereoconservative four-step synthesis starting from hexafluoroacetone protected L-aspartic and L-glutamic acid 2a,b, respectively. Hexafluoroacetone protected ω-isocyanato-α-methylamino acids 4a,b– the key intermediates of the synthesis – are versatile building blocks for amino acid and peptide modification and promising candidates for combinatorial chemistry. Upon reaction with alcohols, compounds 4 give activated N ^ω-urethane protected ω-amino-α-methylamino acid derivatives 5–7; upon reaction with amines, ω-ureido-α-methylamino acid derivatives 10–12 and 3-methylamino-pyrrolidin-2-ones 13 are available. Received November 17, 1999. Accepted November 26, 1999     

Synthesis and calming activity of 6<Emphasis Type="Italic">H</Emphasis>-2-Amino-4-Aryl-6-(4-<Emphasis Type="Italic">β</Emphasis>-D-Allopyranosyloxyphenyl)-1,3-Thiazine

E-(4-β-D-Allopyranosyloxyphenyl)-1-(4-substituted phenyl)propenone derivatives (1a–g) have been synthesized by the Claisen-Schmidt condensation of helicid with 4-substituted acetophenone using 10% NaOH aqueous solution as a catalyst. 6H-2-Amino-4-aryl-6-(4-β-D-allopyranosyloxyphenyl)-1,3-thiazine (2a–g) were synthesized by the 1,4-Michael reaction of 1a–g with thiourea. The structures of all the new products were established by ¹H NMR, IR, and MS spectroscopy. Compound 2b (200 mg·kg^–1) showed better sedative-hypnotic activity, so further modification of helicid should be worthwhile.     

Synthesis and properties of poly(amide–imide)s containing a N-methylcarbazole group

A new dicarboxylic acid monomer containing the N-methylcarbazole and imide structures, 3,6-bis(trimellitimido)-N-methylcarbazole (I), was prepared from the condensation of 3,6-diamino-N-methylcarbazole (c) and trimellitic anhydride. The diamine c was synthesized in three steps starting from the methylation of carbazole, followed by nitration and catalytic hydrazine reduction. A series of N-methylcarbazole-containing poly(amide–imide)s were synthesized by direct polycondensation from the diimide–diacid I with various aromatic diamines. These poly(amide–imide)s had inherent viscosities of 0.66–1.47 dl/g and were readily soluble in a variety of organic solvents, including N-methyl-2-pyrrolidone and N,N-dimethylacetamide (DMAc). Transparent, flexible, and tough films of these polymers could be cast from DMAc solutions, and these films exhibited excellent mechanical strength. The glass-transition temperatures of these poly(amide–imide)s were in the range 317–362 °C. All the poly (amide–imide) did not degrade noticeably below 480 °C in nitrogen, and the 10% weight loss temperatures and char yields at 800 °C were above 520 °C and 60% in nitrogen, respectively, indicating high thermal stability. Received: 8 February 2000/Accepted: 23 March 2000     

Synthesis of 3,6-bisubstituted phenyl-bi-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives

2,5-Bihydrazino-1,3,4-thiadiazole (2) was synthesized by condensation of 2,5-bimercapto-1,3,4-thiadiazole (1) with hydrazine hydrate, and compound 2 reacted with acyl chloride to give 2,5-biacylhydrazino-1,3,4-thiadiazole derivatives (3a–3e). Ring closure of compounds 3a–3e was achieved with POCl3 as the cyclization agent giving 3,6-bisubstituted phenyl-bi-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives (4a–4e), respectively. The novel compounds were identified by elemental analysis, and by infrared (IR), 1H-nuclear magnetic resonance (NMR), and mass (MS) spectrometry. The mechanism of the cyclization is also discussed. __________ Translated from Organic Chemistry, 2006, 26(12): 1720–1722 [译自: 有机化学]     

Palladium-catalyzed amination in the synthesis of macrocyclic compounds containing 1,3-disubstituted adamantane fragments

Palladium-catalyzed amination of 1,3-dibromobenzene, 2,6-dibromopyridine, 3,3′-dibromobiphenyl, 2,7-dibromonaphthalene, and 1,8-dichloroanthracene with an equimolar amount of 2,2′-(adamantane-1,3-diyl)diethanamine resulted in the formation of macrocyclic compounds containing one or several adamantane and one or several aromatic fragments. The reactions of 2,2′-(adamantane-1,3-diyl)diethanamine with excess 1,3-dibromobenzene, 2,6-dibromopyridine, 1,8-dichloroanthracene, and 1,8-dichloroanthraquinone gave the corresponding N,N′-diaryl derivatives. Polyaza macrocycles incorporating adamantane, aromatic, and 4,7,10-trioxatridecane-1,13-diamine fragments, were obtained by palladium-catalyzed amination of the N,N′-diaryl derivatives with 4,7,10-trioxatridecane-1,13-diamine.     

Synthesis and aromatizational rearrangements of new imino-, hydrazono-, and azino-2,5-cyclohexadienylidene systems as ligands for cascade type metallocomplexes

Three approaches to the synthesis ofN-substituted imino-, hydrazono-, and azino-2,5-cyclohexadienylidene systems based on reactions of 4-methyl-4-trichloromethylcyclohexa-2,5-dienone with aminophenols and hydrazones and condensation of hydrazones ofpara-semiquinoid ketones with carbonyl compounds, including that of the ferrocene series, were realized. The latter reaction, when applied to 3,6-dibromophenanthrene-9, 10-quinone, was accompanied by quantitative aromatizational molecular rearrangement with the elimination of the CCl₃ group. Using Rh¹ complexes as an example, it was shown that the heteroorganic ligands obtained can be used for the synthesis of mixed-ligand metallocomplexes with triple coordination of the metal atom including simultaneous metal-ligand interactions of the n-, π-, and σ-types. The principle of metal-ligand “cascade” appeared as a result of the generalization of two new phenomena of organometallic sereodynamics, which we have found recently^2,3 and have called oxidative and reductive redox-rotation. In the “cascade”, type1 (“metal-ligand-metal”) or type2 (“ligand-metal-ligand”) metallocomplexes, one or several coordinated metal ligand”) metallocomplexes, one or several coordinated metal atoms capable of concertedly and reversibly changing their valence in the course of intramolecular conformational transformation are in positions of mutual conjugation. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 363–367, February, 1997.     

Reactions of 3-[N-chloroacetylamino-N-(4-nitrophenyl)]-2-formylindole with alkylamines

The reactions of 3-[N-chloracetylamino-N-(4-nitrophenyl)]-2-formylindole (1a) with 2-(N, N-dialkylamino)ethylamines afford complex condensation products 7b,c consisting of two similar but not identical diazepinoindole fragments. For the reaction of compound 1a with 3-(N,N-diethylamino)propylamine, the process occurs in a different manner, and the predominant product is 4-ethylaminopropyl-1-(4-nitrophenyl)-2-oxo-1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole hydrocloride (14). Two routes of these unexpected transformations were proposed. The structures of the synthesized products were proved by the ¹sH and ¹³C NMR, HMBC, and HSQC (direct proton-carbon correlation) spectra. Dedicated to Academician V. A. Tartakovsky on the occasion of his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1536–1542, August, 2007.     

Experimental and theoretical studies on the functionalization reactions of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic acid and-acid chloride with various aminophenols

The 1H-pyrazole-3-carboxylic acid 1 was converted via reactions of its acid chloride 2 with various aminophenol derivatives 3a--d into the corresponding N-(hydroxyphenyl)-1H-pyrazole-3-carboxamides 4a--d, respectively, in good yields (34–53%). The reactions of 1 or 2 with 3 in benzene or toluene for 5–7 h with no catalytic amounts of base lead to the formation of the products 4. The structures of all new synthesized compounds were established by the ¹³C NMR,¹H NMR, IR, masss spectroscopic data and elemental analyses. The reaction mechanism of 2 with 3 was studied by means of the RHF/3-21G and RHF/6-31G method.     

2-[3-(Trifluoromethyl)phenyl]furo[3,2-b]pyrroles: synthesis and reactions

The synthesis and reactions of methyl 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole-5-carboxylate (1a) are described. Upon reaction with methyl iodide, benzyl chloride, or acetic anhydride, this compound gave N-substituted products 1b-d. By hydrolysis of compounds 1a-c, the corresponding acids 2a-c were formed, or by reaction with hydrazine-hydrate, the corresponding carbohydrazides 3a-c were formed. By heating 2-[3-(trifluoromethyl)phenly]-4H-furo[3,2-b]pyrrole-5-carboxylic acid (2a) in acetic anhydride, 4-acetyl-2-[3-(trifluoromethyl)phenyl]furo[3,2-b]pyrrole (4) was formed. By hydrolysis of 4, 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole (5a) was formed, and reactions with methyl iodide or benzyl chloride gave N-substituted products 5b-c. The reaction of 4 with dimethyl butynedioate gave substituted benzo[b]furan 6. Compound 3a reacted with triethyl orthoesters giving 7a-c, which afforded with phosphorus (V) sulphide the corresponding thiones 8a-c. The thiones 8a-c reacted with hydrazine hydrate to form hydrazine derivatives 9a-c. The reaction of triethyl orthoformiate with compounds 9a-c led to furo[2′,3′: 4,5]pyrrolo[1,2-d][1,2,4]triazolo[3,4-f][1,2,4]triazines 10a-c. Hydrazones 11a-c were formed from 3a-c and 5-[3-(trifluoromethyl)phenyl]furan-2-carboxaldehyde. The effect of microwave irradiation on some condensation reactions was compared with “classical” conditions. The results showed that microwave irradiation shortens the reaction time while affording comparable yields.