Synthesis and antibacterial evaluation of some new 4‐substituted‐3‐aryl‐1‐(2,6‐dimethylpyrimidin‐4‐yl)pyrazoles

Synthesis of a series of new 4‐substituted‐3‐aryl‐1‐(2,6‐dimethylpyrimidin‐4‐yl)pyrazoles ( 2a , 2b , 2c , 2d , 2e , 2f , 2g , 3a , 3b , 3c , 3d , 3e , 3f , 3g , and 4a , 4b , 4c , 4d , 4e , 4f , 4g ) is described. All the synthesized compounds were evaluated in vitro for their antibacterial activity against two gram‐positive and two gram‐negative bacteria, namely, Bacillus subtilis (MTCC 8509), Bacillus stearothermophilus (MTCC 8508), Escherichia coli (MTCC 51), and Pseudomonas putida (MTCC 121), and their activity was compared with two commercial antibiotics, streptomycin and chloramphenicol. Two compounds, namely, 3‐(4‐anisyl)‐1‐(2,6‐dimethylpyrimidin‐4‐yl)pyrazole‐4‐carboxaldehyde ( 2b ) and 3‐(2‐thienyl)‐1‐(2,6‐dimethyl pyrimidin‐4‐yl)pyrazole‐4‐carboxaldehyde ( 2g ) were found to be equipotent to streptomycin and chloramphenicol against gram‐negative bacteria, E. coli having minimum inhibitory concentration (MIC) value = 4 μg/mL. Compounds 4b and 4d also displayed good activity against E. coli with MIC = 8 μg/mL. J. Heterocyclic Chem., (2011).     

Synthesis of 2-(o-chloropheny)- and 2-(2′,6′-dichlorophenyl)-4-formyl-1,2,3-triazoles

Mesoaldehyde 1,3-dioxime was treated with either o-chlorophenyl- or 2,6 dichloro-phenylhydrazine to give the corresponding 2-chlorophenylhydrazone. Hydrazones 1a and 1b were treated with acetic anhydride and cyclized to triazoles ( 3a and 6a ) with cesium carbonate. These were then hydrolized to the previously unknown chlorophenyltriazole aldehydes ( 4a and 4b ). They were also converted to a number of acid derivatives, alcohols, and amines.     

Synthesis of herbicidal 3‐substituted‐4(3H)‐pyrimidinones under high pressure

The reaction of an N‐monosubstituted amidine with a β‐ketoester to afford a pyrimidinone is sluggish at best under normal conditions. We now report that this reaction can be effected in moderate yield under high pressure. Thus, 2,6‐dichloro‐4‐pyridyl‐(N‐prop‐2‐ynyl)carboxamidine (4b) was reacted with three α‐substituted‐β‐ketoesters (2b‐d) at 10–16 kbar to afford herbicidal 2‐(2,6‐dichloro‐4‐pyridyl)‐3‐(prop‐2‐ynyl)‐4(3H)‐pyrimidinones 5b and 5c in 15 ‐ 43% yield. This result expands the scope of reactions promoted by application of high pressure.     

Regioselective intramolecular ring closure of 2-amino-6-bromo-2,6-dideoxyhexono-1,4-lactones to 5- or 6-membered iminuronic acid analogues: synthesis of 1-deoxymannojirimycin and 2,5-dideoxy-2,5-imino-D-glucitol

1-Deoxymannojirimycin (8c) was synthesised from 2-amino-6-bromo-2,6-dideoxy-D-mannono-1,4-lactone (7) by intramolecular direct displacement of the C-6 bromine employing non-aqueous base treatment followed by reduction of the intermediate methyl ester. Likewise, using aqueous base at pH 12, ring closure took place by 5-exo attack on the 5,6-epoxide leading to 2,5-dideoxy-2,5-imino-L-gulonic acid (9b), which was reduced to 2,5-dideoxy-2,5-imino-D-glucitol (9b). The method was further applied to 2-amino-6-bromo-2,6-dideoxy-D-galacto- as well as D-talo-1,4-lactones (14 and 15). However, only the corresponding six-membered ring 1,5-iminuronic acid mimetics, namely (2R,3R,4S,5R)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-D-galactonic acid, 16) and (2S,3R,4S,5R)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-D-talonic acid, 17), were obtained. The corresponding enantiomers, L-galacto- as well as L-talo-2-amino-6-bromo-2,6-dideoxy-1,4-lactones ent-14 and ent-15, reacted accordingly to give the D-galacto- and L-altro-1,5-iminuronic acid mimetics, (2S,3S,4R,5S)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-L-galactonic acid, ent-16) and (2R,3S,4R,5S)-3,4,5-trihydroxypipecolic acids (2,6-dideoxy-2,6-imino-L-talonic acid, ent-17), respectively.     

Synthesis and reactivity of thiophene palladium and thiophene dipalladium complexes with unsaturated molecules

Reactions of 2,5‐dibromothiophene, 1 , with [Pd₂(dba)₃]^?dba [Pd(dba)₂; dba = dibenzylideneacetone] in the presence of N‐donor ligands such as 2,2′‐bipyridine (bpy) and 4,4′‐di‐tert‐butyl‐2,2′‐bipyridine (dtbbpy) give arylpalladium complexes of cis‐[2‐(5‐BrC₄H₂S)PdBrL₂], 2a, b [L₂ = bpy ( 2a ), L₂ = dtbbpy ( 2b )], and cis‐cis‐L₂PdBr[2,5‐(C₄H₂S‐)PdBr(L₂)], 3a, b [L₂ = bpy ( 3a ), L₂ = dtbbpy ( 3b )]. Treatment of cis complexes 2a, b and 3a, b with CO causes the insertion of CO into the Pd? C bond to give the aroyl derivatives of palladium complexes of cis‐[2‐(5‐BrC₄H₂S)COPdBrL₂], 4a, b [L₂ = bpy ( 4a ), L₂ = dtbbpy ( 4b )], and cis‐cis‐[(L₂)(CO)BrPdC₄H₂S‐PdBr(CO)(L₂)], 5a, b [L₂ = bpy ( 5a ) and L₂ = dtbbpy ( 5b )], respectively. Treating complexes 2a, b with 1 mole equivalent of isocyanide XyNC (Xy = 2,6‐dimethylphenyl) gave iminoacyl complexes cis‐[2‐(5‐BrC₄H₂S)C?NXyPdBrL₂], 6a, b [L₂ = bpy ( 6a ), L₂ = dtbbpy ( 6b )], and a 3‐fold excess of isocyanide XyNC (Xy = 2,6‐dimethylphenyl) gave triiminoacyl complexes [2‐(5‐BrC₄H₂S)(C?NXy)₃ PdBr], 7 . Cyclization reactions of 6a, b with 3 mole equivalents of isocyanide XyNC (Xy = 2,6‐dimethylphenyl) or cyclization reaction of 7 with 1 mole equivalent of isocyanide XyNC (Xy = 2,6‐dimethylphenyl) both gave tetraiminoacyl complexes of [2‐(5‐BrC₄H₂S)(C?NXy)₄PdBr], 8 , which was also obtained by the reaction of 1 or 2a, b with a 4‐fold excess of isocyanide XyNC with or without add Pd(dba)₂. Similarly, complexes 3a and b were also reacted with 2 mole equivalents of isocyanide XyNC (Xy = 2,6‐dimethylphenyl) to give iminoacyl complexes cis‐cis‐[(L₂)(CNXy)BrPdC₄H₂S‐PdBr(CNXy)(L₂)], 10a, b [L₂ = bpy ( 10a ), L₂ = dtbbpy ( 10b )] and an 8‐fold excess of isocyanide XyNC (Xy = 2,6‐dimethylphenyl) afforded tetraiminoacyl complexes of [2,5‐(C₄H₂S)(C?NXy)₈Pd₂Br₂], 11 . Complexes 2a, b and 3a, b reacted with TlOTf [(TfO = CF₃SO₃)] in CH₂Cl₂ to give 9a, b and 12a, b , respectively, in a moderate yield. Copyright © 2007 John Wiley & Sons, Ltd.     

Novel,racemic or nearly-racemic antibacterial bromo- and chloroquinols and γ-lactams of the verongiaquinol and the cavernicolin type from the marine sponge Aplysina (= Verongia) cavernicola

Butanolic extracts of the Mediterranean sponge Aplysina (= Verongia) cavernicola have given, by reverse-phase HPLC, the antibacterial quinols (±)-3-bromoverongiaquinol (= (±)-3-bromo-1-hydroxy-4-oxo-2,5-cyclohexadine-1-acetamide; 1d) and (±)-3-bromo-5-chloroverongiaquinol (= (±)-3-bromo-5-chloro-1-hydroxy-4-oxo-2,5-cyclohexadine-1-acetamide; 1c ) besides the products of their formal cyclization 5-chlorohexadiene-1-acetamide; 1c ) besides the products of their formal cyclization 5-chlorocavernicolin (= 5-cloro-3,3a,7,7aβ-tetrahydro-3aβ-hydroxy-2,6(1H)-indoledione; 6) , the C(7)-epimerizing 7β-bromo-5-chlorocavernicolin (=7 β-bromo-5-chloro-3,3a,7,7aβ-tetrahydro-3aβ-hydroxy-2,6(1H)-indoledione; 4a and 7α-bromo-5-chlorocavernicolin (4b) , and the C(7)-epimerizing 5-bromo-7β-chlorocavernicolin ( = 5-bromo-7β-chloro-3,3a,7,7aβ-tetrahydro-3aβ-hydroxy-2,6(1H)-indoledione; 5a) and 5-bromo-7α-chlorocavernicolin (5b) . The latter four were isolated as mixtures of C(7)-epimerizing monoacetates 4a′/4b′ and 5a′/5b′. Both 1 and 1c proved to be racemic from NMR examination of their esterification products with (–)-methyl-oxyacetic acid, whilst 6 had a ca. 6% enantiomeric purity as shown by a ¹H-NMR study of its monoacetate 6′ in the presence of a chiral shift reagent. These chiroptical data of the first chiral quinols from the Verongida and of 6 suggest phenol oxidative routes from tyrosine precursors for their formation. In view of their bioactivities, 1d and 1c have been synthesized from (p-hydroxyphenyl)acetic acid byt phenol oxidative routes.     

Synthesis and spectroscopic properties of some dideuterated cyanopyridines

4‐Cyanopyridine‐2,6‐d₂ ( 5a‐2,6‐d₂ ), 3‐cyanopyridine‐2,6‐d₂ ( 5b‐2,6‐d₂ ), and 2‐cyanopyridine‐4,6‐d₂ ( 5c‐4,6‐d₂ ) were synthesized from the corresponding 2‐, 3‐ or 4‐pyridinecarboxylic acid N‐oxides. These dideuterated products were characterized by their mass and NMR spectra.     

Synthesis of Novel Series of 6‐Chloro‐1,1‐dioxo‐1,4,2‐benzodithiazine Derivatives with Potential Biological Activity

A series of 6′‐chloro‐1′,1′‐dioxo‐2′H‐spiro[benzo[d][1,3,7]oxadiazocine‐4,3′‐(1,4,2‐benzodithiazine)]‐2,6(1H,5H)‐dione derivatives 2a , 2b and 3a , 3b have been synthesized starting from 3‐aminobenzodithiazines 1a , 1b and isatoic anhydride. Subsequent reactions of 2a with 3‐chlorophenyl isocyanate gave condensation products 4 and 5 . Compound 2a was also converted into 3‐(2‐aminobenzamido)‐6‐chloro‐7‐methyl‐1,1‐dioxo‐1,4,2‐benzodithiazine derivatives 6 , 7 , 8 , 9 , 10 . The mechanisms of the reactions are discussed.     

Synthesis and characterization of a series of 2‐aminopyridine nickel(II) complexes and their catalytic properties toward ethylene polymerization

A series of 2‐aminopyridine Ni(II) complexes bearing different substituent groups {(2‐PyCH₂NAr)NiBr, Ar = 2,4,6‐trimethylphenyl ( 3a) , 2,6‐dichlorophenyl ( 3b ), 2,6‐dimethylphenyl ( 3c) , 2,6‐diisopropylphenyl ( 3d ), 2,6‐difluorophenyl ( 3e ); (2‐PyCH₂NHAr)₂NiBr₂, Ar = 2,6‐diisopropylphenyl ( 4a )} have been synthesized and investigated as precatalysts for ethylene polymerization in the presence of methylaluminoxane (MAO). High molecular weight branched polymers as well as short‐chain oligomers were simultaneously produced with these complexes. Enhancing the steric bulk of the ortho‐aryl‐substituents of the catalyst resulted in higher ratio of solid polymer to oligomer and higher molecular weight of the polymer. With ortho‐haloid‐substitution, the catalysts afforded a product with low polymer/oligomer ratio ( 3b ) and even only oligomers ( 3e ) in which C₁₄H₂₈ had the maximum content. Compared with complex 3d containing ionic ligand, complex 4a containing neutral ligand exhibited obviously low catalytic activity for ethylene polymerization. The molecular weight, molecular weight distribution, and microstructure of the resulted polymer were characterized by gel permeation chromatography and ¹³C NMR spectrogram. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1618–1628, 2008     

Der Einbau von Magnesium in Liganden der Chlorophyll-Reihe mit (2,6-Di-t-butyl-4-methylphenoxy)magnesiumjodid

Introduction of Magnesium into Ligands of the Chlorophyll Series by (2,6-Di-t-butyl-4-methylphenoxy)magnesium Iodide Experimental details are given for the new method of introducing magnesium into porphinoid ligands by (2,6-di-t-butyl-4-methylphenoxy)magnesium iodide (1) , previously published in preliminary form [1]. Besides magnesium octaethylporphyrinate (14) , methyl pyrochlorophyllide a (10) , methyl chlorophyllide a (8) , and methyl bacteriochlorophyllide a (12) , the complexation of pheophytin a (2) to chlorophyll a (3) and of pheophytin b (4) to chlorophyll b (5) are described.     

Synthesis and configuration of trans-1-amino-4-benzyl-2,6-dimethylpiperazine as an intermediate of semi-synthetic rifamycins

The synthesis of trans-1-amino-4-benzyl-2,6-dimethylpiperazine (1b), trans-4-benzyl-2,6-dimethylpiperazine (VIIb) and trans-2,6-dimethylpiperazine (IIb) are described, by condensation of N-benzyl-1,2-propanediamine with α-bromopropionate and successive thermal cyclization and reduction with lithium aluminum hydride. The assignment of the cis, trans configuration to the isomers was based on a thorough examination of the ring proton nmr signals of the two isomers of 4-benzyl-2,6-dimethylpiperazine (VIIa and VIIb) interpreted in terms of conformational considerations.     

Synthesis of Novel Bis[(5‐cyanopyridin‐6‐yl)sulfanyl]butanes,Bis(2‐S‐alkylpyridines), and Bis(3‐aminothieno[2,3‐b]pyridines) Incorporating 2,6‐Dibromophenoxy Moiety

The synthetic precursors pyridine‐2(1H)‐thiones 2a , b and bis(pyridine‐2(1H)‐thione) derivative 4 , using aldehydes 1a , b incorporating 2,6‐dibromophenoxy moiety, were prepared and used to synthesize the novel target materials bis[(5‐cyanopyridin‐6‐yl)sulfanyl]butanes 5a , b , bis(2‐S‐alkylpyridines) 8a , b , and bis(3‐aminothieno[2,3‐b]pyridines) 13a–c through facile procedures. Characterization of the newly prepared compounds via elemental analyses and spectral data is established.     

Bildung von 4-, 5- und 6gliedrigen Heterocyclen durch ambidoselektive Ringschlüsse von Enolat-Ionen

Formation of 4-, 5- and 6-membered heterocycles by ambidoselective cyclization of enolate anions N-Acylmethyl-N-chloracetyl-2,6-dimethylanilines 4 were cyclized with base to 4-, 5- or 6-membered ring compounds, depending on the substituent R² (Scheme 2). All products can be rationalized as derived from the intermediate enolate anions a and b . The enolate anion a reacts by intramolecular alkylation to yield either 1, 4-oxazines 5 or azetidines 6 (Schemes 1, 3 and 7). The regioselectivity observed is expected on the basis of the allopolarization principle. The enolate anion b reacts only with formation of a new C? C bond (Scheme 5). Comparison with the behaviour of the 2, 6-unsubstituted anilines 9, 1a and 12 , shows a strong dependence not only on electronic but also on steric factors (Scheme 4 and 6).     

Facile and convenient synthesis of 2,6-disubstituted 4H-1,3-oxazin-4-one derivatives

Facile and convenient methods for the preparation of a variety of 2,6-disubstituted 4H-1,3-oxazin-4-ones 3 by three complementary methods are described. Treatment of the branched aliphatic imidate 2c,d with diketene 1 in the presence of a catalytic amount of acetic acid affords 2-substituted 6-methyl-1,3-oxazin-4-ones 3c,d , whereas the unbranched imidate 2b,e gave oxazines 3b,e and pyrimidines 4b,e (Method A). The reaction of acyl Meldrum's acid 5 with imidate 2 afford 2,6-disubstituted oxazine 3, though the alkylimidate with acetyl Meldrum's acid yielded 3 and 5-acetyl-1,3-oxazine-4,6-dione 8 (Method B). The cylodehydration of acylacetylcarboxamide 13 with acid, such as 70% perchloric acid or fluorosulfonic acid, afforded 1,3-oxazines 3 (Method C).     

1,3-Dipolar cycloaddition reactions of isothiazol-3(2H)-ones with nitrile oxides. An unexpected site selectivity of the carbonyl bond of 5-benzoyl-isothiazol-3(2H)-one

2,6-Dichlorobenzonitrile oxide ( 2a ) reacts with isothiazolones 1a and 1b at the ethylenic double bond to give 4 via transformation of the primary cycloadducts 3 . Mesitonitrile oxide ( 2b ) adds preferentially to the carbonyl double bond of 1b yielding the monoadduct 5 and the bisadduct 6 .     

Isolation and Structural Study on Carbohydrates from Cynanchum otophyllum and Cynanchum paniculatum

Three new carbohydrates were isolated from the acidic hydrolysis part of the ethyl acetate extract of Cynanchum otophyllum Schneid (Asclepiadaceae) and one new carbohydrate from the ethyl acetate extract of Cynanchum paniculatum Kitagawa. Their structures were determined as methyl 2,6-dideoxy-3-O-methyl-α-D-arabino-hexopyranosyl-(1 → 4)-2,6-deoxy-3-O-methyl-β-D-arabino-hexopyranosyl-(1 → 4)-2,6-dideoxy-3-O-methyl-α-D-arabino-hexopyranoside (1), ethyl 2,6-dideoxy-3-O-methyl-β-D-ribo-hexopyranosyl-(1 → 4)-2,6-dideoxy-3-O-methyl-α-l-lyxo-hexopyranoside (2), met hyl 2,6-dideoxy-3-O-methyl-α-l-ribo-hexopyranosyl-(1 → 4)-2,6-dideoxy-3-O-methyl-β-D-lyxo-hexopyranosyl-(1 → 4)-2,6-dideoxy-3-O-methyl-α-D-arabino-hexopyranoside (3), and 2,6-dideoxy-3-O-methyl-β-D-ribo-hexopyranosyl-(1 → 4)-2,6-dideoxy-3-O-methyl-α-d-arabino-hexopyranosyl-(1 → 4)-2,6-dideoxy-3-O-methyl-α -d-arabino-hexopyranose (4), respectively, by spectral methods.     

Tetraarylpentaborates, [B(5)O(6)Ar(4)](-) (Ar = C(6)H(4)OMe-4, C(6)H(3)Me(2)-2,6): their formation from the reaction of arylboronic acids with an aryloxorhodium complex,structure, and chemical properties

The reactions of (4-methoxyphenyl)boronic acid (1a) and of (2,6-dimethylphenyl)boronic acid (1b) with (PMe(3))(3)Rh-(OC(6)H(4)Me-4) (2) in a 5:1 molar ratio result in the formation of cationic rhodium complexes with new tetraarylpentaborates [Rh(PMe(3))(4)](+)[B(5)O(6)Ar(4)](-) (3a, Ar = C(6)H(4)OMe-4; 3b, Ar = C(6)H(3)Me(2)-2,6). The characterization of 3a is as follows: orthorhombic space group P2(1)2(1)2(1), a = 14.7600(5) A, b = 17.1675(5) A, c = 19.8654(5) A; V = 5033.7(3) A(3); Z = 4. The characterization of 3b is as follows: orthorhombic space group Pnma, a = 23.704(6) A, b = 17.254(8) A, c = 13.304(2) A; V = 5441(2) A(3); Z = 4. An intermediate complex, [Rh(PMe(3))(4)](+)[Ph(3)B(3)O(3)(OC(6)H(4)Me-4)](-) (4), was isolated from the reaction of phenylboroxine, (PhBO)(3), with 2. The tetraarylpentaborates smoothly undergo hydrolysis to give [Rh(PMe(3))(4)](+)[B(5)O(6)(OH)(4)](-) (5).     

1,3-bis(2,4,6-trinitrophenylaminooxy)propane and its 4-cyano-2,6-dinitrophenyl congener: Synthesis and properties

Starting from N-hydroxyphthalimide (5) and 1,3-dibromopropane (6) we obtained 1,3-bis(phthalimidooxy)propane (7) which led to 1,3-bis(aminooxy)propane dihydrochloride (8). From its reaction with picryl chloride or 4-cyano-2,6-dinitrochlorobenzene, the two title compounds (4b, 4a) were obtained. ¹H-NMR and ¹³C-NMR spectra are presented. For comparison with the analogous N-methoxy-2,6-dinitro-4-R-anilines 1a, 1b (R=CN or R=NO₂), wer report the hydrophobic characteristics (by RPTLC), electronic spectra for the neutral compounds and their anions, pK _a values, and the behavior towards oxidizers (DPPH, PbO₂, Pb(CH₃COO)₄, KMnO₄ and Ag₂O); DPPH converts compounds 1a, 1b and 4a, 4b into betainic structures 2a, 2b respectively.     

Stereoselective synthesis of 2-substituted 6-[1-(2,6-difluorophenyl)ethyl]-5-methylpyrimidin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones

A procedure has been proposed for the synthesis of 2-(cyclopentylsulfanyl)-6-[(1R)-1-(2,6-difluorophenyl) ethyl]-5-methylpyrimidin-4(3H)-one through intermediate (3R)-4,4-dimethyl-2-oxotetrahydrofuran-3-yl (2R)-2-(2,6-difluorophenyl)propanoate which was obtained from prochiral 2-(2,6-difluorophenyl)prop-1-en-1-one generated in situ. The proposed procedure may be regarded as stereoselective route to 6-[(1R)-1-(2,6- difluorophenyl)ethyl]-5-methylpyrimidin-4(3H)-one derivatives.     

A study on chemical behaviors of some 4‐pyrones synthesized by one‐step reactions towards various amines

Cycloaddition of acetylbenzoyl ketene generated in situ as an intermediate during one‐step reaction between excess benzoylacetone and oxalylchloride to C=C double bond of cyclic enol form of benzoylacetone gave 3‐acetyl‐5‐benzoyl‐6‐methyl‐2‐phenyl‐4(4H)‐pyrone 1a . Condensation reactions of 1a together with 3,5‐dibenzoyl‐2,6‐diphenyl‐4(4H)‐pyrone 1b and 3‐benzoyl‐5‐ethoxycarbonyl‐2,6‐diphenyl‐4(4H)‐pyrone 1c with two‐fold excess primary amines provided a series of 3‐benzoyl‐1‐alkyl‐5‐(1‐alkylimino‐ethyl)‐6‐phenyl‐2‐methyl‐4(1H)‐pyridinone 2 , 3,5‐dibenzoyl‐1‐alkyl‐2,6‐diphenyl‐4(1H)‐pyridinone 3a‐c and 3‐benzoyl‐1‐alkyl‐5‐ethoxycarbonyl‐2,6‐diphenyl‐4(1H)‐pyridinone 3d,e derivatives, respectively. In addition, while prolonged reaction of n‐pentylamine with unsymmetrical pyrone derivative 1a gives a symmetrical pyridinone derivative namely 3,5‐dibenzoyl‐2,6‐dimethyl‐1‐pentyl‐4(1H)‐pyridinone 5 , much prolonged action n‐pentylamine and then aqueous n‐pentylamine on 1b resulted in degradation of the 4‐pyrone ring to give dibenzoylmethane.