Catalytic oxidative degradation of s-triazine and phenoxyalkanoic acid based herbicides with metalloporphyrins and hydrogen peroxide: Identification of two distinct reaction schemes

Oxidative degradation of the herbicides atrazine (1), atraton (2), ametryn (3) and mecoprop (4), was carried out with hydrogen peroxide and metalloporphyrins as catalysts. Two different reaction conditions were studied, the first involving Mn(TDCPP)Cl in an aprotic solvent with buffer (S-I), and the second using Fe(TPFPP)Cl in a protic solvent (S-II). Reaction products were characterized, and based on these it is shown that there are two distinct reaction schemes.In the case of the S-I conditions, it is suggested that the s-triazines were oxidized through hydroxylation of the alkyl side chains followed by dealkylation, while S-II was ineffective for these reactions. In contrast, mecoprop, was oxidized with high efficiency by S-II, leading to decarboxylation and further oxidation, while in the presence of S-I, low substrate conversion was observed, and reaction resulted mainly from oxidation at the benzyl position. Sulfoxidation of ametryn was observed with both systems.The different reactivity shown by the two systems supports the involvement of different reactive species, which we assign to the oxo and hydroperoxy complexes. These routes show similarities with metabolic pathways, with the reactivity pattern of S-I analogous to the reported metabolism of these pollutants with cytochrome P450 enzymes, while S-II catalyses mecoprop decarboxylation via a similar pathway to that seen with peroxidase catalysed reactions.     

Asymmetric synthesis of substituted 1-aminocyclopropane-1-carboxylic acids from a new chiral glycine equivalent with 3,6-dihydro-2H-1,4-oxazin-2-one structure

Condensation of the new chiral glycine equivalent 10 with aldehydes at room temperature in the presence of K₂CO₃ under solid–liquid phase-transfer-catalysed conditions afforded stereoselectively new chiral (Z)-α,β-didehydroamino acid (DDAA) derivatives with oxazinone structure 14. These systems have been used in diastereoselective cyclopropanation reactions for the synthesis of enantiomerically pure 1-aminocyclopropanecarboxylic acids (ACCs) such as (−)-allo-norcoronamic and (−)-allo-coronamic acids.     

Reactions of N,N-diisopropyl-2-aminoethylp-fluorobenzene thiosulfonate with oxidising agents

The behaviour of N,N-diisopropyl-2-aminoethyl p-fluorobenzene thiosulfonate 3, which may be considered as a weakly toxic chemical analogue of VX agent, was investigated against oxidising agents. As VX 1, this compound exhibits the same tendency to give S–S bond cleavage. Its degradation by Curox® shows the formation of the N-oxide 6 which subsequently gives the sulfonate 7 by hydrolysis. The action of hydrogen peroxide, with or without boric acid, leads to the sulfinate 4 by S-S bond cleavage. Its oxidation gives sulfonate 7. Finally, reactions of MMPP and m-CPBA afford sulfonate 7 but no intermediates are highlighted with these reagents.     

Alkali-metal mediated zincation of N-heterocyclic substrates using the lithium zincate complex, (THF)Li(TMP)Zn(tBu)2 and applications in in situ cross coupling reactions

This study investigates the ability of the mixed-metal reagent [Li(TMP)Zn(tBu)₂] 1 to promote direct Zn-H exchange reactions (zincations) of a wide range of N-heterocyclic molecules. The generated metallated intermediates from these reactions are intercepted with I₂ and some of them are also employed as precursors in Pd-catalysed Negishi cross-coupling applications. A comparison with recent precedents in metallation chemistry reveals that for some of these heterocycles, 1 allows improved conversions, under milder conditions and in certain cases, even gives unique regioselectivities.     

Oxidation of aryl-substituted allylic alcohols by an optically active Fe(III)(porph*) catalyst: enantioselectivity,diastereoselectivity and chemoselectivity in the epoxide versus enone formation

A set of aryl-substituted allylic alcohols (±)-2 was oxidized using the chiral Fe(porph*) complex 1 as the catalyst and iodosyl benzene (PhIO) as the oxygen source. Whereas one enantiomer of the allylic alcohol 2 is preferentially epoxidized to give the threo- or cis-epoxy alcohol 3 (up to 43% e.e.) as the main product (d.r. up to >95:5), the other enantiomer of 2 is enriched (up to 31% e.e.). Some non-stereoselective allylic oxidation to give the enone 4 also takes place. The observed diastereo- and enantioselectivities in the epoxidation reactions are rationalized in terms of a synergistic interplay between the hydroxy-directing effect and the steric interactions of the catalyst 1 and the substrate 2.     

Palladium(II)-N-heterocyclic carbene complex derived from proline towards Suzuki-Miyaura coupling reaction in water at room temperature

Palladium(II)-N-heterocyclic carbene complex 1 derived from proline has been proved to be a highly effective catalyst in the Suzuki-Miyaura coupling reaction of aryl iodides and bromides with arylboronic acids in water at room temperature. The reactions are tolerant towards various functional groups in the substrates. Moreover, the complex 1-catalyzed medium-scale (10.0 mmol) Suzuki-Miyaura reactions were also carried out and it was found that the complex was also effective enough in these cases.     

First synthesis of α-(3-R-1-adamantyl)sulfoacetic acids and their derivatives

By sulfonation of 3-R-1-adamantylacetic acids 1 with H₂SO₄ in trifluoroacetic anhydride (TFAA), the previously unknown α-(3-R-adamantyl)sulfoacetic acids 2 were obtained. In the case of 1-adamantylacetic acid 1a, the use of ～1 equiv of H₂SO₄ led to only 1-adamantylacetic acid 2a, while with an excess of the reactant the hydroxylation of the adamantane tertiary C–H bond also occurred. It is assumed that the bis(trifluoroacetyl)sulfate generated in situ from H₂SO₄ and TFAA is responsible both for sulfonation and oxidation steps. The adamantylated sulfoacetic acids were used for the preparation of a series of derivatives by modifications of carboxylic, sulfonic acid, and tertiary adamantane OH-groups. Due to the use of TFAA as a medium, a series of derivatives of sulfoacetic acids was obtained directly from acids 1 within one-pot procedures. Some of the synthesized compounds possess anti-HSV activity.     

Synthesis of heparin saccharides—V : Anomeric o-benzyl derivatives of l-idopyranosyluronic acid

Derivatives of the anomeric benzyl l-idopyranosides and l-idopyranosiduronates have been synthesized from d-glucose as models for conformation studies. The two key reactions in the synthesis are: (a) inversion of configuration at C(5) of the d-glucofuranose derivative 4, and (b) catalytic oxidation of the l-idopyranosides 19, and 22 to uronic acids.     

Synthesis and chiral recognition abilities of new calix[6]arenes bearing amino alcohol moieties

Herein the synthesis and recognition abilities towards amino acids and amino alcohols of new d-/l-phenylalaninol substituted p-tert-butylcalix[6]arenas are reported. These compounds, 6 and 7 have been synthesized via nucleophilic substitution reactions involving 5,11,17,23,29,35-tert-butyl-37,38-dimethoxy-39,40,41,42-(p-tosylethoxy)calix[6]arene 5 with d-/l-phenylalaninol in dry THF. The extraction properties of 6 and 7 towards some selected amino acid methylesters and amino alcohols have been studied by liquid–liquid extraction. These results show that chiral calix[6]arene derivatives exhibit a good affinity towards all amino acids and amino alcohols.     

Antiradical activity of morpholine- and piperazine-functionalized triphenylantimony(V) catecholates

The antiradical activity of the functionalized triphenylantimony(V) catecholates Ph₃Sb[4-O(CH₂CH₂)₂N-3,6-DBCat] (I), Ph₃Sb[4,5-Piperaz-3,6-DBCat] (II), and Ph₃Sb[4-PhN(CH₂CH₂)₂N-3,6-DBCat] (III) (where [4-O(CH₂CH₂)₂N-3,6-DBCat]^2?, [4,5-Piperaz-3,6-DBCat]^2?, and [4-PhN(CH₂CH₂)₂N-3,6-DBCat]^2? are the dianionic ligands 3,6-di-tert-butyl-4-(morpholin-1-yl)-, 3,6-di-tert-butyl-4,5-(piperazine-1,4-diyl)-, and 3,6-di-tert-butyl-4-(4-phenylpiperazin-1-yl)catecholates, respectively) was studied in reactions with the diphenylpicrylhydrazyl radical during autooxidation of unsaturated fatty (oleic and linoleic) acids with lipid peroxidation of Russian sturgeon (Acipenser gueldenstaedti B.) sperm and human blood erythrocytes in vitro as examples. The EC₅₀ and n _DPPH values obtained indicate the high antiradical activity of complexes II and III in the reactions with the stable radical. On the whole, complexes I–III inhibit the lipid peroxidation in both model (oxidation of unsaturated fatty acids) and in vitro experiments. The inhibiting effects of the complexes are comparable with and even, in some cases, higher than those of the known antioxidant ionol.     

Synthesis and properties of 3-arylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-diones and related compounds: photo-induced autorecycling oxidation of some amines

Novel 3-phenyl- and 3-(4-nitrophenyl)cyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-diones and the corresponding imino derivatives 5a,b and 6a,b were synthesized in modest to moderate yields by the abnormal and normal aza-Wittig reaction of 2-(1,3-diazaazulen-2-ylimino)triphenylphosphorane with aryl isocyanates and subsequent heterocyclization reaction with a second isocyanate. The related cationic compound, 1-methyl-3-phenylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-dionylium tetrafluoroborate 7a, was also prepared. The electrochemical reduction of these compounds exhibited more positive reduction potentials as compared with those of the related compounds of 3,10-disubstituted cyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1H,3H)-dione systems. In a search of the oxidizing ability, compounds 5a, 6a, and 7a were demonstrated to oxidize some amines to give the corresponding imines in more than 100% yield under aerobic and photo-irradiation conditions, while even benzylamine was not oxidized under aerobic and thermal conditions at 100 °C. The oxidation reactions by cation 7a are more efficient than that by 5a and 6a. Quenching of the fluorescence of 5a was observed, and thus, the oxidation reaction by 5a probably proceeds via electron-transfer from amine to the excited singlet state of 5a. In the case of cation 7a, the oxidation reaction is proposed to proceed via formation of an amine-adduct of 7a and subsequent photo-induced radical cleavage reaction.     

Towards lignin-protein crosslinking: amino acid adducts of a lignin model quinone methide

The polyaromatic structure of lignin has long been recognized as a key contributor to the rigidity of plant vascular tissues. Although lignin structure was once conceptualized as a highly networked, heterogeneous, high molecular weight polymer, recent studies have suggested a very different configuration may exist in planta. These findings, coupled with the increasing attention and interest in efficiently utilizing lignocellulosic materials for green materials and energy applications, have renewed interest in lignin chemistry. Here we focus on quinone methides (QMs)—key intermediates in lignin polymerization—that are quenched via reaction with cell-wall-available nucleophiles. Reactions with alcohol and uronic acid groups of hemicelluloses, for example, can lead to lignin-carbohydrate crosslinks. Our work is a first step toward exploring potential QM reactions with nucleophilic groups in cell wall proteins. We conducted a model compound study wherein the lignin model compound guaiacylglycerol-β-guaiacyl ether 1, was converted to its QM 2, then reacted with amino acids bearing nucleophilic side-groups. Yields for the QM-amino acid adducts ranged from quantitative in the case of QM-lysine 3, to zero (no reaction) in the cases of QM-threonine (Thr) 10 and QM-hydroxyproline (Hyp) 11. The structures of the QM-amino acid adducts were confirmed via 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and density functional theory (DFT) calculations, thereby extending the lignin NMR database to include amino acid crosslinks. Some of the QM-amino acid adducts formed both syn- and anti-isomers, whereas others favored only one isomer. Because the QM-Thr 10 and QM-Hyp 11 compounds could not be experimentally prepared under conditions described here but could potentially form in vivo, we used DFT to calculate their NMR shifts. Characterization of these model adducts extends the lignin NMR database to aid in the identification of lignin-protein linkages in more complex in vitro and in vivo systems, and may allow for the identification of such linkages in planta.     

A study on synthesis and antimicrobial activity of 4-acyl-pyrazoles

4-Acyl-pyrazole-3-carboxylic acids (1) were synthesized via the reaction of 4-acyl-2,3-furandiones (F) with hydrazone (1-benzylidene-2-(2,5-dimethyl-phenyl)-hydrazine) by heating under solid phase and their acid chlorides (2) were obtained. Then these derivatives were easily converted into the corresponding derivatives such as ester, amide, ureide, pyrazolo-pyridazine, etc. Totally 62 new compounds were synthesized. The structures of these new synthesized compounds were determined by spectroscopic methods and the in vitro antibacterial activity of newly synthesized compounds were carried out against some gram-positive and gram-negative bacteria by well diffusion method (zone inhibition). Our results have showed that these new synthesized compounds have much potent of antibacterial activity owing to containing of pyrazole and/or pyridazine, chromone, oxazine, furane, and pyrrole rings. Some of the new pyrazole derivatives exhibited higher activities than reference drugs against the representative bacteria.     

Enantioselective synthesis of epimeric cis-3-carboxycyclopentylglycines

Two epimeric chiral cyclopentylglycines (−)-16 and (+)-17, functionalised with a carboxy group cis to the amino acid group, were prepared starting from chiral 2-amino-3-oxo-norbornanecarboxylic acid derivative exo-9 by combining two classical reactions such as the Diels–Alder and retro-Claisen reactions. Compounds 16 and 17 are non-proteinogenic amino acids of biological interest containing conformational constraints in which the skeletons of both 2-aminoadipic acid and 2-aminopimelic acid are included.     

A tandem decarboxylation and inverse electron-demand Diels-Alder reaction of amino-thiophenecarboxylic acids with 1,3,5-triazines

The scope of 1,3,5-triazine inverse electron-demand Diels-Alder (IDA) reactions was expanded to include aminothiophenecarboxylic acids as latent dienophiles. A series of 2-amino-3-thiophenecarboxylic acids (1a-d) and a 3-amino-2-thiophenecarboxylic acid (5) were introduced as productive dienophiles in IDA reactions with various 1,3,5-triazines (2a-e). This method is useful for the one-step synthesis of both thieno[2,3-d]pyrimidines and thieno[3,2-d]pyrimidines, which should complement existing methods.     

Nitrile biotransformations for the practical synthesis of highly enantiopure azido carboxylic acids and amides, ‘click’ to functionalized chiral triazoles and chiral β-amino acids

Under very mild conditions, biotransformations of racemic azido nitriles using Rhodococcus erythropolis AJ270, a nitrile hydratase/amidase-containing microbial whole-cell catalyst, afforded highly enantiopure, (R)-α-arylmethyl- and (+)-α-cyclohexylmethyl-β-azidopropanoic acids and their (S)- and (−)-carboxamide derivatives in excellent yields. The resulting functionalized chiral organoazides were converted in a straightforward fashion to a pair of antipodes of α-benzyl-β-amino acids (R)-13 and (S)-13. Azido carboxamide (S)-11a and azido carboxylic acid (R)-12a underwent ‘click’ reactions with diethyl acetylenedicarboxylate and phenylacetylene to produce functionalized chiral triazoles 14 and 15, respectively. The easy preparation of the starting nitrile substrates, highly efficient and enantioselective biotransformation reactions, and versatile utility of the resulting functionalized azido carboxylic acids and amide derivatives, render this method very attractive and practical in organic synthesis.     

On the dimers of β-tocopherol

Upon oxidation in aprotic media, β-tocopherol (2) forms a spiro-dimer (10) as the main product. The reaction mechanism is a hetero-Diels-Alder process with inverse electron demand of two intermediate ortho-quinone methide molecules. The spiro-dimer can be reduced to the corresponding symmetric ethano-dimer (11). In contrast to the well-studied α-tocopherol case, spiro-dimer and ethano-dimer do not form a reversible redox pair, their interconversion is accompanied by coupling reactions at C-7 with 7a-(β-tocopher-5a-yl)-β-tocopherol (13) as the main byproduct besides some oligomeric material. The full NMR assignments (¹H, ¹³C) of the β-tocopherol oxidation products are given.     

The (butadiene)zirconocene route to active homogeneous olefin polymerization catalysts

(Butadiene)zirconocene is observed to exist as an equilibrium mixture of (s-cis-) and (s-trans-η⁴-C₄H₆)ZrCl₂ isomers. The system adds a variety of unsaturated organic reagents to form metallacyclic (allyl)metallocene products. In some cases, a second equivalent of a reagent is taken up, which forms the basis of a variety of useful template coupling reactions of butadiene at the bent metallocene framework. The Lewis acid B(C₆F₅)₃ adds to (butadiene)zirconocene and to a great variety of butadiene complexes of ansa-metallocenes and related systems to give zwitterionic metallocene-butadiene-borate betaines. Most of these systems are active homogeneous Ziegler-Natta olefin polymerization catalysts, that do not require additional activation. Catalyst activities are often in a similar range to those observed for other catalyst activation procedures used in this chemistry. In the case of the (butadiene)metallocene/B(C₆F₅)₃ systems we can often observe the first olefin insertion step. This feature was utilized to carry out a variety of mechanistic studies of the essential carbon-carbon coupling steps that take place at such bent metallocene catalyst systems. Even reactions with the functionalized monomer methylmetacrylate could be followed in this way. Some chelate ligand late metal systems were also included in these studies. However, these systems mostly behaved differently, even in cases where some structural similarities were observed.     

Asymmetric syntheses of piperidino-benzodiazepines through ‘cation-pool’ host/guest supramolecular approach and their DNA-binding studies

The asymmetric synthetic approach to piperidino-benzodiazepine 4a (a homolog of DC-81) has been developed. The absolute stereochemistry of 4 and 5 has been assigned to be (S) at C-12a position. This procedure features the use of a ‘cation-pool’ strategy and also a host/guest supramolecular co-catalysis approach. In this study, the chloroformate of 8-phenylmenthyl has been employed as a chiral auxiliary and includes one-pot conditions for anodic oxidation, which are followed by nucleophilic addition to an N-acyliminium ion. In addition, intramolecular azido reductive-cyclization and nitro reductive dithioacetal deprotective tandem-cyclization approaches have also been utilized for the syntheses of these compounds 4a,b and 5a,b. Some of the representative compounds exhibited an enhanced DNA-binding ability in comparison to the natural product DC-81.     

Chemoenzymatic synthesis of both enantiomers of 3-hydroxy- and 3-amino-3-phenylpropanoic acid

Ethyl (S)-3-hydroxy-3-phenylpropionate (S)-2 was obtained by the asymmetric reduction of ethyl 3-phenyl-3-oxopropionate 1 with the yeast Saccharomyces cerevisiae (ATCC 9080). The kinetic resolution of racemic ethyl 2-acetoxy-3-phenyl-propionate rac-3 with the same microorganism, gave after hydrolysis ethyl (R)- and (S)-3-hydroxy-3-phenylpropionates (R)-2 and (S)-2 which were converted by a straightforward series of reactions to the enantiomers of 3-amino-3-phenyl-propionic acids (S)-6 and (R)-6. The asymmetric reduction and hydrolytic kinetic resolution were also tested with several other whole cell systems under a variety of conditions.