5257-06-7

2-Aminoacetophenone (AAP) was recognized as the key compound for the so-called untypical aging off-flavor (UTA) in Vitis vinifera wines. In this study, it was shown that AAP can be formed by photooxidation of free and protein-bound tryptophan (TRP) in combination with a subsequent storage in model wine. Solutions of TRP and lysozyme were exposed to artificial sunlight both in the presence and in the absence of the photosensitizer riboflavin. Aliquots of the irradiation batches were stored in model wine solutions containing tartaric acid, sulfite and ethanol in different combinations. AAP formation could be identified from both free and bound (lysozyme) TRP, while free TRP resulted in higher yields. The presence of riboflavin during irradiation generally favored the AAP formation. AAP formation increased with increasing irradiation times, but AAP was not detectable, if TRP was directly incubated in model wine. Not only the irradiation time but also the storage time of model wines favored the formation of AAP. Concerning the model wine composition, it became evident that the presence of tartaric acid resulted in the highest AAP formation during storage.

A metal-free method for the synthesis of heterodifunctional indole derivatives is developed through TBHP/KI-mediated oxidative coupling. The reaction constructs C-O and C-C bonds in succession with the help oftert-butyl peroxy radicals generated by the TBHP/KI catalytic system, enabling the direct realization of the heterodifunctionalization of indole in one pot. The product of this reaction is a novel heterodifunctional compound. This work might provide a new effective method for the synthesis of polycyclic indole compounds.

Binding of 3-methylindole (3-MI) to the surface of colloidal CdS particles modifies their luminescence Behaviour so that the trapped electron and hole generated upon photoirradiation are scavenged by adsorbed O2 and 3-MI to yield 2-acetylformanilide and 2-aminoacetopnenone.

The oxidative cleavage of indoles (Witkop oxidation) involving the use of H2O2 or urea hydrogen peroxide in combination with a polar solvent has been described. Among these solvents, 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) stands out as the one affording the corresponding 2-ketoacetanilides generally in higher yields The protocol described has also enabled the oxidation of different pyrroles and furans derivatives. Furthermore, the procedure was implemented in a larger-scale and HFIP was distilled from the reaction mixture and reused (up to 4 cycles) without a significant detriment in the reaction outcome, which remarks its sustainability and applicability. (Figure presented.).

Direct C-H silylation of quinoxalinones was achieved by the combination of organic photoredox catalysis and hydrogen atom transfer (HAT) under ambient air conditions. Transition metal- and external oxidant-free conditions were the major features of this protocol. A series of silylated quinoxalinones with broad functional groups had been synthesized in moderate to high yields. This methodology was also applicable for the C-H silylation of some electron-deficient heteroarenes.

Chlorophyll is the most abundant photocatalytic pigment that enables plants to absorb solar energy and convert it to energy storage molecules. Herein, we report a tandem photocatalytic approach utilizing the natural pigment chlorophyll in crude form to achieve photoinduced electron transfer (PET) and energy transfer (EnT) towards the oxidative functionalization of indoles. Redox potentials, ESR, fluorescence quenching and UV experiments have evidenced the dual catalytic activity of chlorophyll. The highlight of the study is the auto-tandem photocatalytic role of chlorophyll to enable the green oxidation of indoles using molecular oxygen as the oxidant, water as the reaction medium, and photochemical energy from the visible region of the spectrum.

Herein, we present an expedient Cu-catalyzed [5 + 1] cyclization of 2-alkynylanilines and ClCF2COONa to divergent construction of N-(quinolin-2-yl)amides and quinolin-2(1H)-ones by regulating the reaction solvents. Notably, nitrile acts as a solvent and performs the Ritter reactions. ClCF2COONa is used as a C1 synthon in this transformation, which also represents the first example for utilization of ClCF2COONa as an efficient desiliconization reagent. The current protocol involves in situ generation of isocyanide, copper-activated alkyne, Ritter reaction and protonation.

A selective functionalization of C-C-C bonds toward N-C-O bonds is realized by an n-Bu4NI-catalyzed reaction of 3-methylindoles with primary amines using TBHP as the unique oxidant. The systematic process involves oxygenation, nitrogenation, ring-opening, and recyclization, affording a broad range of quinazolinones in good to excellent yields.

Dearomatisation of indole derivatives to the corresponding isatin derivatives has been achieved with the aid of visible light and oxygen. It should be noted that isatin derivatives are highly important for the synthesis of pharmaceuticals and bioactive compounds. Notably, this chemistry works excellently with N-protected and protection-free indoles. Additionally, this methodology can also be applied to dearomatise pyrrole derivatives to generate cyclic imides in a single step. Later this methodology was applied for the synthesis of four pharmaceuticals and a pesticide called dianthalexin B. Detailed mechanistic studies revealed the actual role of oxygen and photocatalyst.

Tryptophan oxidation in biology has been recently implicated in a vast array of paramount pathogenic conditions in humans, including multiple sclerosis, rheumatoid arthritis, type-I diabetes, and cancer. This 2,3-dioxygenative cleavage of the indole ring of tryptophan with dioxygen is mediated by two heme enzymes, tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO), during its conversion to N-formylkynurenine in the first and rate-limiting step of kynurenine pathway. Despite the pivotal significance of this enzymatic transformation, a vivid viewpoint of the precise mechanistic events is far from complete. A heme superoxide adduct is thought to be the active oxidant in both TDO and IDO, which, following O-O bond cleavage, presumably generates a key ferryl (FeIV=O) reaction intermediate. This study, for the first time in model chemistry, demonstrates the potential of synthetic heme superoxide adducts to mimic the bioinorganic chemistry of indole dioxygenation by TDO and IDO, challenging the widely accepted categorization of these metal adducts as weak oxidants. Herein, an electronically divergent series of ferric heme superoxo oxidants mediates the facile conversion of an array of indole substrates into their corresponding 2,3-dioxygenated products, while shedding light on an unequivocally occurring, putative ferryl intermediate. The oxygenated indole products have been isolated in a?31% yield, and characterized by LC-MS, 1H and 13C NMR, and FT-IR methodologies, as well as by 18O2(g) labeling experiments. Distinctly, the most electron-deficient superoxo adduct is observed to react the fastest, specifically with the most electron-rich indole substrate, underscoring the cruciality of electrophilicity of the heme superoxide moiety in facilitating the initial indole activation step. Comprehensive understanding of such mechanistic subtleties will benefit future attempts in the rational design of salient therapeutic agents, including next generation anticancer drug targets with amplified effectivity.

Heme active sites are capable of oxidizing organic substrates by four electrons using molecular oxygen (heme dioxygenases), where a dioxygen (O2) adduct of heme (FeIII-O2-) acts as the primary oxidant, in contrast to monooxygenases, where high-valent species are involved. This chemistry, although lucrative, is difficult to access using homogeneous synthetic systems. Over the past few years using a combination of self-assembly and in situ resonance Raman spectroscopy, the distribution of different reactive intermediates formed during the electrochemical reduction of oxygen has been elucidated. An FeIII-O2- species, which is the reactive species of dioxygenase, is an intermediate in heterogeneous electrochemical O2 reduction by iron porphyrins and its population, under electrochemical conditions, may be controlled by controlling the applied potential. Iron porphyrins having different axial ligands are constructed on a self-assembled monolayer of thiols on an electrode, and these constructs can activate O2 and efficiently catalyze the dioxygenation of 3-methylindole and oxidation of a series of organic compounds having C-H bond energies between 80 and 90 kcal mol-1 at potentials where FeIII-O2- species are formed on the electrode. Isotope effects suggest that hydrogen-atom transfer from the substrate is likely to be the rate-determining step. Axial thiolate ligands are found to be more efficient than axial imidazoles or phenolates with turnover numbers above 60000 and turnover frequencies over 60 s-1. These results highlight a new reaction engineering approach to harness O2 as a green oxidant for efficient chemical oxidation.

Incorporation of water has been revealed to successfully facilitate visible-light photoredox catalysis of indole leading to increased production of C2-quaternary indolinone. The water-promoted photoreaction of indole under catalyst-free conditions by a household compact fluorescence light was also demonstrated. The antiproliferative activity of the synthesized indolinones was evaluated against three human cancer cell lines.

A new synthetic protocol has been developed for the synthesis of N-formamide derivatives using ethers as a C1 synthon under metal-free reaction conditions. The reaction is proposed to proceed through C?H functionalization, C?O cleavage, and C?N bond formation. This protocol is applicable to a variety of primary amines resulting in N-formamides in moderate to good yields. 1,4-dioxane was chosen as best C1 synthon after screening with various ethers. Mechanistic studies disclosed that the reaction proceeds through a radical pathway. While using α-amino ketones a α-alkylation product was formed rather than formylation. By replacing dioxane with Tetramethylethylenediamine (TMEDA) under standard conditions also gave the N-formamide derivatives in moderate yields. (Figure presented.).

A method for N-formylating an amine that includes reacting the amine and a formamide compound in the presence of a phosphonic anhydride to form an N-formylated amine. The phosphonic anhydride is present in an amount of 5-100 mol % relative to a total number of moles of the amine, and the reacting is performed for 1-24 hours at a temperature of 45-100° C.

An unprecedented chemoselective double annulation of α-trifluoromethylated isocyanides with o-acylaryl isocyanides has been developed. This new reaction provides a rapid, efficient, and complete atom-economic strategy for the synthesis of trifluoromethylated oxadiazino[3,2-α]indoles in a single operation from readily available starting materials. Isocyanide insertion into C=O double bonds is disclosed for the first time as indicated by the results of 18O-labeling experiment. A mechanism for this domino reaction is proposed involving chemoselective heterodimerization of two different isocyanides, followed by indole-2,3-epoxide formation and rearrangement.

A photoinduced oxidative formylation of N,N-dimethylanilines with molecular oxygen in the absence of an external photocatalyst was developed and provided the corresponding formamides in good yields under mild reaction conditions. Investigations indicated that both the starting material and product act as photosensitizers and that 1O2 coexists with O2?- during the reaction through energy transfer and single electron transfer process.

A metal-free catalytic approach to tryptanthrins has been achieved for the first time. The unique process is realized by an organocatalytic and indole and anthranilic acid substrate co-catalyzed photochemical oxidative condensation with visible light and O2. The truly environmentally friendly reaction conditions enable various reactants to participate in the process to deliver structurally diverse tryptanthrins.

Simple ion exchange of the chloride anion of an ionic-liquid-functionalized magnetic nanoparticle with [PdCl4]2- provided a highly water-dispersible and magnetically separable palladium catalyst that exhibited excellent activity toward transfer hydrogenation reactions in water as a solvent. The catalyst demonstrated outstanding performance in aqueous-phase transfer hydrogenation of various nitroarenes in a highly chemo- and regioselective manner by using HCOONH4 as a low-cost, green, and easily available hydrogen donor. Also, by using only 0.25 mol % of the catalyst and formic acid as both a hydrogen donor and formylating agent, the catalyst showed excellent activity in the one-pot, direct synthesis of N-arylformamides from nitroarenes in water as a solvent. Notably, owing to the presence of a hydrophilic ionic liquid on the surface of silica-coated iron oxide nanoparticles, the catalyst showed highly stable dispersion in water, as evidenced by the zeta potential and extremely low affinity to the organic phase. These features make this catalyst system suitable for an efficient double-separation strategy (successive extraction/final magnetic separation). The recovered aqueous phase containing the catalyst can be simply and efficiently reused in eight runs without a decrease in activity and can be easily separated from the aqueous phase at the end of the process by applying an external magnetic field.

Photocontact allergy is a well-known side effect of topical preparations of the nonsteroidal anti-inflammatory drug ketoprofen. Photocontact allergy to ketoprofen appears to induce a large number of photocross allergies to both structurally similar and structurally unrelated compounds. Contact and photocontact allergies are explained by structural modification of skin proteins by the allergen. This complex is recognized by the immune system, which initiates an immune response. We have studied ketoprofen's interaction with amino acids to better understand ketoprofen's photoallergenic ability. Irradiation of ketoprofen and amino acid analogues resulted in four different ketoprofen photodecarboxylation products (6-9) together with a fifth photoproduct (5). Dihydroquinazoline 5 was shown to be a reaction product between the indole moiety of 3-methylindole (Trp analogue) and the primary amine benzylamine (Lys analogue). In presence of air, dihydroquinazoline 5 quickly degrades into stable quinazolinone 12. The corresponding quinazolinone (17) was formed upon irradiation of ketoprofen and the amino acids N-acetyl-l-Trp ethyl ester and l-Lys ethyl ester. The formation of these models of an immunogenic complex starts with the ketoprofen-sensitized formation of singlet oxygen, which reacts with the indole moiety of Trp. The formed intermediate subsequently reacts with the primary amino functionality of Lys, or its analogue, to form a Trp-Lys adduct or a mimic thereof. The formation of a specific immunogenic complex that does not contain the allergen but that can still induce photocontact allergy would explain the large number of photocross allergies with ketoprofen. These allergens do not have to be structurally similar as long as they can generate singlet oxygen. To the best of our knowledge, there is no other suggested explanation for ketoprofen's photoallergenic properties that can account for the observed photocross allergies. The formation of a specific immunogenic complex that does not contain the allergen is a novel hypothesis in the field of contact and photocontact allergy.

2-Isocyanoacetophenone (3a) was found to be an easily accessible starting material for the unexpected formation of various heterocyclic systems. Thus, a hitherto unknown rather unstable 4-methylene-4H-benzoxazine derivative 4, which could be characterized by NMR spectroscopy, was formed in situ by the reaction of 3a in the presence of weak acids. In the presence of benzylamines, a new class of 3,4-dihydroquinazoline derivatives 6 and their oxidation products, quinazolin-4-ones 9, were obtained. The starting materials and products were completely characterized by spectroscopic and X-ray analysis. The scope and limitations of these cyclization reactions were investigated under various reaction conditions. High-level quantum chemical calculations were carried out to elucidate the mechanisms leading to scaffolds 4 and 6. The calculations suggest that the formation of 4 and 6 involves the generation of an unusual six-membered N-heterocyclic carbene or its C-protonated form as a reaction intermediate, followed by tautomerisation. This mechanism might also be applicable to other isocyanide cyclization reactions. Copyright

An efficient and selective Pd(0)-catalyzed sp3 C-H bond arylation-oxidation of 4-methylquinazolines is reported. The method enables the introduction of arylketone at the benzylic position of 4-methylquinazolines without the use of an additional directing group, and atmospheric oxygen is used as the sole oxidant.

A simple and efficient protocol for N-formylation of aliphatic and heterocyclic amines has been described with formic acid in the absence of catalyst and solvent.

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The reaction of a-substituted 2-isocyanostyrenes, which could be readily prepared from commercially available 2-aminophenyl ketones or 2-aminobenzonitriles, with sulfur in the presence of a catalytic amount of selenium proceeded smoothly to give the corre

Alky, aryl, and heteroaryl amines were found to react efficiently with formic acid under Lewis acid catalysis giving N-formyl derivatives in high yields. A study of ZnCl2-catalyzed N-formylation of a variety of amines using formic acid as formylating agent is described.

2-(1-Alkoxyalkyl)-4-alkylidene-4H-3,1-benzoxazines are conveniently prepared by the reaction of 1-(2-isocyanophenyl) ethanones or 1-(2-isocyanophenyl)propan-1-ones with a vinyl ether, such as 2-methoxypropene or ethyl vinyl ether, in the presence of a catalytic amount of (±)-camphor-10-sulfonic acid. Georg Thieme Verlag Stuttgart.

(Chemical Equation Presented) A mild, one-pot synthesis of 4-quinolones is described. Under the optimal conditions, a variety of 2-substituted 4-quinolones were synthesized via sequential palladium-catalyzed amidation of 2′-bromoacetophenones followed by base-promoted intramolecular cyclization.

N-Formylation of anilines has efficiently been carried out at room temperature in excellent yields by treatment with formic acid in polyethylene glycol (PEG-400). No additional solvent and catalyst are required.

We have developed a novel method for the oxidative cleavage of indole carbon double bonds in the presence of H2O2 using plant cell cultures as peroxidase. The oxidative method has some advantage, as features such as mild reactions, good yields, easy work-up and safety.

Little is known about the HRP-mediated oxidations of 3-alkylindoles. Whereas 3-methylindole and 3-ethylindole were found to be turned over smoothly by HRP, reactions of tryptophol and N-acetyltryptamine were inefficient. Oxidations of the former two indoles by HRP under aerobic conditions led to the corresponding ring-opened o-acylformanilides and oxindoles, whereas anaerobic oxidations resulted in oxidative dimerization. The major products of anaerobic oxidation of 3-methylindole were shown to be two hydrated dimers, while anhydrodimers were obtained in the 3-ethyl case. The proposed mechanism involves HRP-mediated one-electron oxidation to give an indole radical that either dimerizes (anaerobic conditions) or reacts with O2 (aerobic conditions). Measured kinetics of indole oxidation by HRP compounds I and II mirrored their relative reactivities under turnover conditions. The observed comparable binding affinities for all four indole substrates investigated suggest that the low reactivity of tryptophol and N-acetyltryptamine reflect binding to HRP in an orientation that is disadvantageous to electron transfer oxidation of the indole ring.

We have developed a mild procedure for the oxidative cleavage of indole carbon double bonds using plant cell cultures as a catalytic system in the presence of H2O2. We have developed a novel procedure for the oxidative cleavage of indole carbon double bonds in the presence of H 2O2 using plant cell cultures as a catalytic system. The oxidative procedure has some advantages, such as mild reactions, good yields, easy work-up and safety.

Sodium iodide in acidic media has been employed for the synthesis of N-arylformamides and N-arylacetamides. The NaI/acetic acid reagent system has also been extended for the synthesis of 1,4-benzodiazepine-2,5-diones, pyrrolo[2,1-c][1,4]benzodiazepine-5,11-diones, and fused [2,1-b]quinazolinones.

2,4-Disubstituted quinolines have been synthesized by reactions of o-isocyano-β-methoxystyrenes, which can be easily prepared from commercially available o-aminophenyl ketones in three steps, with alkyl(or aryl)lithiums in generally good yields. Subsequently, o-isocyano-β- methoxystyrenes have also proved to react efficiently with lithium dialkylamides to afford the corresponding 4-substituted N,N-dialkylquinolin-2-amines in satisfactory yields. Graphical Abstract.

Alkyl(or aryl)lithiums reacted efficiently with o-isocyano-β-methoxystyrene derivatives, prepared in three steps from o-aminophenyl ketones, to afford the corresponding 2,4-disubstituted quinolines in satisfactory yields.

Kynurenine (1) and indole-3-acetic acid (2) are considered as potential precursors of 2-aminoacetophenone (3), which is regarded to be the aroma impact compound causing an "untypical aging off-flavor" (UTA) in Vitis vinifera wines. The mechanism of the formation of 3 was studied using model fermentation and model sulfuration media spiked with 1 or 2 as potential precursors. Possible degradation products such as kynurenamine (4) and kynurenic acid (5), or skatole (6), 2-oxoskatole (7), 2-formamidoacetophenone (8), 2-oxindole-3-acetic acid (9), and 3-(2-formylaminophenyl)-3-oxopropionic acid (10) were evaluated by HPLC-UV of the fermentation and sulfuration media and comparison with synthesized 7, 8, 9, and 10. The synthesis of the possible precursor 4-(2-aminophenyl)-2,4-dioxobutanoic acid (11), a proposed metabolite of 1 failed because a spontaneous cyclization yields 5 and N-oxo-kynurenic acid (12), but not 11. It could be shown that the formation of 3 is triggered by an oxidative degradation of 2 after sulfuration with potassium bisulfite via the intermediates 10 and 8. However, no formation of 3 occurred during sulfuration of a model wine spiked with 1 or during fermentation of a model must spiked with 1 or 2.

Indoleacetic acid was oxidized under oxygen atmosphere by the crude enzyme solution prepared by blending rice husk in buffer solution of pH 7.3. The major oxidation products (3, 4, and 5), characterized by physical and chemical methods, showed little effects on germination and growth of lettuce seeds while IAA inhibited completely the germination at 5 ppm. This evidence suggests that the amounts of IAA in embryos decreases due to the oxidation by water soluble oxidation enzyme existing in rice husk. The decrease of IAA may be related, in some aspect, to dormancy breaking and also preharvest sprouting of rice seeds. The synthesis and optical resolution of 2 was also achieved.

Starting with the tosylated enaminone 5, the novel quinolone derivatives 3, 8, 9, and 10 were formed by reactions with acetic acid, sulfuryl chloride, and thionyl bromide, respectively.Alkylation of the sulfur-bridged bisquinolone 8 yields the N-substitut

Oxygenation of tryptophan analogues, 2-(3-indolyl)acetic acid (1), 3-(3-indolyl)propionic acid (2), N-benzoyl-L-tryptophan (3), N-tert-butoxycarbonyl-L-tryptophan (4), and N-benzoyl-L-tryptophan n-butylamide (5), with potassium superoxide (KO2) in dimethyl sulfoxide have been studied.In the case of 1, the major products were 2-formylaminobenzoic acid (25.3percent) and 2'-formylaminoacetophenone (18.0percent), which were produced by the secondary oxidation of 3-(2-formylaminophenyl)-3-oxopropionic acid.The reaction of 2 with O2- afforded 4-(2-formylaminophenyl)-4-oxobutanoic acid as the major product (43.3percent), and 2-(3-dioxindolyl)acetic acid (14.5percent) was also obtained.The reaction of 3 and 4 afforded 2-benzoylamino-4-(2-formylaminophenyl)-4-oxobutanoic acid (42.1percent) and 2-tert-butoxycarbonylamino-4-(2-formylaminophenyl)-4-oxobutanoic acid (95.7percent) as the major products, respectively.In the case of 3, 1-benzoyl-2-carboxy-3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrroloindole (27.4percent) was also obtained.Unlike 3 and 4, the reaction of 5 mainly afforded N-n-butyl-2-benzoylamino-3-(3-dioxindolyl)propanamide (15) (52.4percent).We found that 1-n-butyl-2-oxo-3-benzoylamino-4a-hydroxy-1,2,3,4,4a,9,9a-heptahydropyridoindole is a precursor of 15.A similar difference in the reactivity between 3, 4, and 5 was also observed for two tryptophan-containing dipeptides, N-acetyl-glycyl-L-tryptophan and N-acetyl-L-tryptophylglycine.

Highly reactive titanium on graphite as the reagent of choice promotes intramolecular McMurry type reactions of acyloxy- and acylamido carbonyl compounds affording furans, benzofurans and indoles in good to excellent yields.A variety of reducible groups in the substrates is tolerated (e.g. -F, -Cl, -Br, -I, -CF3, -OMe, -CN, -thiophenyl, -COOR, -CONR2) and strained products such as 11h can be obtained, the X-ray analysis of which is reported.The experimental results indicate the possible formation of dianions from the aromatic aldehydes or ketones as reactive intermediates which attack the ester or amide functions in their proximity, rather than a radical path via ketyls.

By pulse or gamma radiolysis in the presence of Br-, 1-methylindole (1b) is oxidized to its radical cation (2b), which adds to (1b) to form a radical dimer (8b).Species (2b) also reacts with OH- to yield the pseudo-base, proposed to be the C2-OH adduct (4b).Identical end-product yields and spectral comparison reveal that the addition of OH. radicals to (1b) also produces (2b) and (4b) but virtually no other OH. adducts to (1b).The selectivity of OH towards the C2 position appears to apply to the other indoles as well.The neutral indolyl radicals (3) disappear both by coupling and dismutation.Discrimination between these modes is governed by the substituent.A methyl group at the C3 position favours C3-C3' coupling.Molecular oxygen adds to neutral indolyl radicals at the C3 position.The measured and estimated rates of O2 addition relate to the redox potentials of the indolyl radicals.The reaction between O2-. and the indolyl radical cation (2) produces (1) and O2.On the other hand, O2-. couples to (3) to yield C3-OOH hydroperoxides (14).The latter decompose into C2-C3 opened amides (13) with concomitant chemiluminescence.

In its reaction with indoles the CCl3O2 radical adds predominantly to the C(2)-C(3) double bond.Only a minor fraction accounts for one-electron oxidation.The 3-adduct undergoes rapid cleavage along the peroxidic bond while several rearrangement paths are

Bis(salicylidene)ethylenediaminatocobalt(II) solubilized in a micellar system, such as 3 percent aq. sodium dodecylsulfate, catalyzed oxygenation of indoles at highly diluted concentrations of the substrate, resulting in a high rate of acceleration and/or reaction selectivity which are attributable to the condensation effect and/or distribution effect of micelles.KEYWORDS - biomimetic oxygenation; micelle; sodium dodecylsulfate; cobalt(II) schiff's base; indole derivative

The reaction of indoles with copper(II) chloride has been studied in acetonitrile.At low copper(II):indole ratios, dimers are formed in the presence of dioxygen, oxygenated products are obtained, and at large copper(II):indole ratios, pyrrole ring-chlorinated products are formed in yields of up to 92percent.The reactions are postulated to proceed via the radical cations of the indoles formed in an electron-transfer reaction.

The oxygenated dimer (2a) of 3-methylindole, which was isolated from the reaction mixture obtained by oxygenation of 3-methylindole in the presence of N,N'-(cis-1,2-cyclohexylene)bis(3-tert-butylsalicylideneaminato)cobalt(II) in chloroform, was shown to be the stereoisomer of 5aβ(H),11aα(H)-12β-hydroxy-10bβ,12α-dimethyl-5a,10b,11a,12-tetrahydro-6H-oxazolodiindole (1a) with inverted configuration at the C12 atom, on the basis of (1)H-and (13)C-nuclear magnetic resonance (NMR) spectroscopic and chemical evidence.Kinetic parameters of restricted rotation about the amide bond in N-acetylated derivatives of 1a and 2a calculated from their dynamic NMR spectra were ΔH*298=20.2+/-0.2 and ΔS*298=+7.8+/-0.5 for the former, and ΔH*298=19.7+/-0.2 kcal mol-1 and ΔS*298=+5.9+/-0.6 calK-1mol-1 for the latter.Acid decomposition of both dimers, 1a and 2a, afforded 3,3'-dimethyl-1-(2'-indolyl)-oxindole, resulting from ring cleavage at the ether bond followed by dehydration.Keywords - 3-methylindole; oxygenation; dimerization; 6H-oxazolodiindole; 1-(2'-indolyl)oxindole; (1)H-NMR; (13)C-NMR; dynamic NMR

Six derivatives of N,N'-ethylenebis(3-tert-butylsalicylideneaminato)cobalt(II), abbreviated as Co(Busalen), were prepared by varying the diamine moiety with ethylenediamine, (R)-1,2-propanediamine, (2S,3S)-2,3-butanediamine, meso-2,3-butanediamine, (1R,2R)-1,2-cyclohexanediamine, and cis-1,2-cyclohexanediamine.The spectral and electrochemical properties of the complexes are reported.These complexes and four derivatives of N,N'-ethylenebis(salicylideneaminato)cobalt(II), Co(salen), were used as catalysts for the oxygenation of 3-methylindole.With increasing steric hindrance of the metal complex catalyst, the rate of the steady-state consumption of the substrate increased, and the induction period increased with increasing steric hindrance at the apical region of Co(Busalen) derivatives.A linear relationship was found between the logarithm of the rate constants and the half-wave potentials for Co(II/III) couples: log(1E2k/mol-1dm-3s-1)=a(E1/2/V)+b, where a and b are 5.2 and -0.56 for the Co(Busalen) series, and 5.5 and -1.25 for the Co(salen) series, respectively.Based on these observations, it is concluded that the catalysis is controlled by the redox potential and tert-butyl groups of the Co(Busalen) derivatives, and the activation of the substrate, not dioxygen is the critical step of this reaction.Keywords - N,N'-ethylenebis(salicylideneaminato)cobalt(II) derivative; 3-methylindole; oxygenation; catalysis; half-wave potential; structure-activity relationship

The factors which govern the induction period in the catalysis of 3-methylindole oxygenation by the title complexes were investigated.Electron spin resonance measurements showed that the superoxo-cobalt complex observed in the induction period disappeared at the start of the steady-state consumption and that the superoxo complex was preferentially converted to a cobalt(II)-substrate complex.During the induction period, the cobalt(II) complexes are converted to cobalt(III) species via their dioxygen adducts in the presence of dioxygen and the substrate, 3-methylindole.For the steady state, a mechanism is proposed which involves a cobalt(III)-anion complex as the catalytic species; facile oxygen introduction takes place at the coordinated deprotonated substrate.

Porphyrins reveal novel functions by metal complex formation.In this lecture following work in our laboratories is described: (1) oxygen binding and activation function of heme (porphyrin Fe(II) complex), (2) monooxygenation function of porphyrin oxovanadium complex (cytochrome P-450 mimic), and (3) catalytic function of porphyrin cobalt complex for valence isomerization (quadricyclanes to norbornadienes).

In the Co(Salen)-catalyzed oxygenolysis of 3-methylindole giving rise to o-formyl-aminoacetophenone, the actual active catalyst species has been found to be the Co(III)-(Salen) complex of an anion of the product.The catalysis involves activation of the substrate but not molecular oxygen.The activation of the substrate involves the rate determining proton transfer from the substrate to the product anion in the coordination sphere of the catalyst.

The reaction of indoles (1) with superoxide ion resulted in ring cleavage to give o-formyl and o-acylaminoketones (6) or N-acylanthranilic acid (8) and ring expansion yielding 2-quinolones (7).All reactions are chemiluminescent except that of 2-methylindole (1h), which gave a coupled product (9).

Oxidative cleavage of 3-methylindole using a catalytic amount of copper (II) salts with added pyridine under an oxygen atmosphere was studied.Smooth cleavage of 3-methylindole took place to give 2-formamidoacetophenone in 73-80percent yield, whereas exclusive formation of a hydrate compound derived from 3,3'-dimethyl-3,3'-bi-3H-indole resulted under anaerobic conditions.Clean oxidative cleavage of N-acetyltryptamine, methyl 3-indolylacetate, and methyl 2-acetamido-3-(3-indolyl)propionate was also achieved, constituting a mimic of tryptophan-2,3-dioxygenase.