Zwitterionic mechanisms for photooxygenation reactions of n-activated c-c double bonds: full geometry optimizations of the diradical and zwitterionic intermediates by ab initio SCF method

Geometry optimizations of perepoxide, 1,4-diradical, zwitterion and dioxetane for the 1,1-diaminoethylene plus singlet molecular oxygen system were performed using the energy gradients of the HF 4-31G and STO-3G solutions. The zwitterion (ZW) is more stable than the perepoxide and σπ-diradical (DR) intermediates (at the 4-31G level), supporting the previous ZW mechanism for photoovygenation reactions of N-activated C-C double bonds     

Synthesis of new unsymmetrical 4,5-dihydroxy-2-imidazolidinones. Dynamic NMR spectroscopic study of the prototropic tautomerism in 1-(2-benzimidazolyl)-3-phenyl-4,5-dihydroxy-2-imidazolidinone

The acid-catalyzed cyclocondensation in refluxing acetonitrile of aqueous glyoxal with N-heteroaryl-N'-phenylureas 4a-f (heteroaryl = 2-thiazolyl, 2-pyrimidinyl,2-pyrazinyl, 2-pyridinyl, 3-pyridinyl and 2-benzimidazolyl) led to the formation of the corresponding 1-heteroaryl-3-phenyl-4,5-dihydroxy-2-imidazolidinones 5a-f. All the products were characterized by elemental and spectroscopic analyses. The free-energy barrier (Delta G not equal) for prototropic tautomerism in 1-(2-benzimidazolyl)-3-phenyl-4,5-dihydroxy-2-imidazolidinone (5f) was determined by dynamic NMR studies to be 81 +/- 2 KJ mol(-1).     

Unusual pathway of the reaction of 4-benzoyl-5-phenylfuran-2,3-dione with acetylmethylenetriphenylphosphorane and methyl triphenylphosphoranylideneacetate

4-Benzoyl-5-phenylfuran-2,3-dione reacts with acetylmethylenetriphenylphosphorane or methyl triphenylphosphoranylideneacetate to form 1:1 adducts of 4-benzoyl-2-hydroxy-2-(2-oxopropyl)-5-phenyl-furan-3(2H)-one or methyl 4-benzoyl-2-hydroxy-3-oxo-5-phenyl-2,3-dihydrofuran-2-ylacetate, respectively, with triphenylphosphine oxide. Structural features of the products are discussed.     

1-甲基-2-苯基吲哚的琥红敏化单重态氧反应

1-甲基-2-苯基吲哚(1)在甲醇中的琥红(RB)敏化单重态氧反应生成1-甲基-2-甲基氧-2-苯基-1, 2-二氢-3H-吲哚-3-酮(4)和1-甲基-2-羟基-2-苯基-1, 2-二氢-3H-吲哚-3-酮(6), 后者在强碱性介质下发生苯乙醇酸型重排生成1-甲基-3-羟基-3-苯基氧化吲哚(14)。研究了6的溶剂分解反应以及外加碱对光氧化反应的影响。探讨了光氧化产物的形成途径。结果表明: 4系两性离子中间体2的溶剂捕获、脱水产物, 而6则系二氧杂环丁烷中间体7的裂解、抽氢产物。     

龙脑烯醛同单重态氧反应的立体选择性

用竹红菌甲素匹配高压钠灯光敏氧化龙脑烯醛,高产率并有立体选择性地获得反应主产物,α-(2,2-二甲基-3-亚甲基-4-羟基-1-环戊烷基)乙醛。反应具有协同的“ene”反应特性。反应的立体选择性被龙脑烯醛的分子构象,取代基的空间位阻效应和烯丙基氢的轴向定位所控制。羰基同环戊烯基的相互隐蔽的分子构象对反应的立体选择性起关键作用。     

Density functional theory study on a missing piece in understanding of heme chemistry: the reaction mechanism for indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase

Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are heme-containing dioxygenases and catalyze oxidative cleavage of the pyrrole ring of L-tryptophan. On the basis of three recent crystal structures of these heme-containing dioxygenases, two new mechanistic pathways were proposed by several groups. Both pathways start with electrophilic addition of the Fe(II)-bound dioxygen concerted with proton transfer (oxygen ene-type reaction), followed by either formation of a dioxetane intermediate or Criegee-type rearrangement. However, density functional theory (DFT) calculations do not support the proposed concerted oxygen ene-type and Criegee-type rearrangement pathways. On the basis of DFT calculations, we propose a new mechanism for dioxygen activation in these heme systems. The mechanism involves (a) direct electrophilic addition of the Fe(II)-bound oxygen to the C2 or C3 position of the indole in a closed-shell singlet state or (b) direct radical addition of the Fe(III)-superoxide to the C2 position of the indole in a triplet (or open-shell singlet) state. Then, a radical-recombination or nearly barrierless charge-recombination step from the resultant diradical or zwitterionic intermediates, respectively, proceeds to afford metastable dioxetane intermediates, followed by ring-opening of the dioxetanes. Alternatively, homolytic O-O bond cleavage from the diradical intermediate followed by oxo attack and facile C2-C3 bond cleavage could compete with the dioxetane formation pathway. Effects of ionization of the imidazole and negatively charged oxyporphyrin complex on the key dioxygen activation process are also studied.     

Dye-sensitized photo-oxygenation of 1,2-cyclohexanediones

The dye-sensitized photo-oxygenation of the enols of 1,2-cyclohexanedione (1) has been carried out in various solvents at -70°-40°. Singlet oxygen is involved in the reaction as evidenced by quenching and rate enhancement observed in deuterated methanol. The reaction proceeds by an ene reaction with singlet oxygen to afford the hydroperoxide, 4, which closes to a five-membered endoperoxide, 5, as a major path or to dioxetane (6) as a minor one. The endoperoxide, 5, decomposed to 5-oxoalkanoic acid (2) with evolution of carbon monoxide or was trapped by the solvent (MeOH or EtOH) to give methyl or ethyl 5-carboxy-2-hydroxypentanoate (3). Competition between the enol of 3-methyl-1,2-cyclohexanedione (1a) and 2,3-dimethyl-2-butene (TME) has shown that the enol is as reactive as TME toward singlet oxygen.     

Structural effects on the OH-promoted fragmentation of methoxy-substituted 1-arylalkanol radical cations in aqueous solution: the role of oxygen acidity

A kinetic and product study of the OH- -induced decay in H2O of the radical cations generated from some di-and tri-methoxy-substituted 1-arylalkanols (ArCH(OH)R*+) and 2- and 3-(3,4-dimethoxyphenyl)alkanols has been carried out by using pulse- and gamma-radiolysis techniques. In the 1-arylalkanol system, the radical cation 3,4-(MeO)2C6H3CH2-OH*+ decay at a rate more than two orders of magnitude higher than that of its methyl ether; this indicates the key role of the side-chain OH group in the decay process (oxygen acidity). However, quite a large deuterium kinetic isotope effect (3.7) is present for this radical cation compared with its a-dideuterated counterpart. A mechanism is suggested in which a fast OH deprotonation leads to a radical zwitterion which then undergoes a rate-determining 1,2-H shift, coupled to a side-chain-to-ring intramolecular electron transfer (ET) step. This concept also attributes an important role to the energy barrier for this ET, which should depend on the stability of the positive charge in the ring and, hence, on the number and position of methoxy groups. On a similar experimental basis, the same mechanism is suggested for 2,5-(MeO)2C6H3CH2OH*+ as for 3,4-(MeO)2C6H3CH2OH*+, in which some contribution from direct C-H deprotonation (carbon acidity) is possible. In fact, the latter process dominates the decay of the trimethoxylated system 2,4,5-(MeO)3C6H2CH2-OH*+, which, accordingly, reacts with OH- at the same rate as that of its methyl ether. Thus, a shift from oxygen to carbon acidity is observed as the positive charge is increasingly stabilized in the ring; this is attributed to a corresponding increase in the energy barrier for the intramolecular ET. When R=tBu, the OH- -promoted decay of the radical cation ArCH(OH)R*+ leads to products of C-C bond cleavage. With both Ar = 3,4- and 2,5-dimethoxyphenyl the reactivity is three orders of magnitude higher than that of the corresponding cumyl alcohol radical cations; this suggests a mechanism in which a key role is played by the oxygen acidity as well as by the strength of the scissile C-C bond: a radical zwitterion is formed which undergoes a rate-determining C-C bond cleavage, coupled with the intramolecular ET. Finally, oxygen acidity also determines the reactivity of the radical cations of 2-(3,4-dimethoxyphenyl)ethanol and 3-(3,4-dimethoxyphenyl)propanol. In the former the decay involves C-C bond cleavage, in the latter it leads to 3-(3,4-dimethoxyphenyl)propanal. In both cases no products of C-H deprotonation were observed. Possible mechanisms, again involving the initial formation of a radical zwitterion, are discussed.     

Hydrogen bonding interactions in α-substituted cinnamic acid ester derivatives studied by FT–IR spectroscopy and calculations

Intermolecular hydrogen bonding interactions in stereoisomeric α-substituted cinnamic acid methyl esters (methyl 2,3-diphenylpropenoate, methyl 2-phenyl-3-(2′-methoxyphenyl)-propenoate, methyl 2-(2′-methoxyphenyl)-3-phenylpropenoate and methyl-2,3-bis(2′-methoxyphenyl)-propenoate) were studied by FT–IR spectroscopy and model calculations at the semi-empirical quantum chemical level of theory. Intermolecular hydrogen bonds of C–H…O types were found to be general in the solid state, but rare in solution. In this hydrogen bond the carbon may be part of either aromatic ring or the olefinic bond. The hydrogen bond acceptor may be the carbonyl oxygen or the oxygen in the methoxy substituent. Modeling helped in determining probable hydrogen bonding sites and their positions and provided with approximate geometric parameters (bond lengths and angles). Pointing out differences between the stereoisomers was also possible.     

Stereoselective Methods for the Synthesis of 4-Benzoyl-1-benzoylamino-3-(2-chlorophenyl)-2-cyano-1-methylthio-1-butene and Its Structure

Selective methods were developed for the synthesis of 4-benzoyl-1-benzoylamino-3-(2-chlorophenyl)-2-cyano-1-methylthio-1-butene on the basis of the reaction of N-methylmorpholinium and piperidinium 5-benzoyl-4-(2-chlorophenyl)-3-cyano-6-hydroxy-6-phenyl-1,4,5,6-tetrahydropyridine-2-thiolates with methyl iodide. The structure of the product was established by X-ray crystallographic analysis.     

Oxidative ring-opening of rel-(2R,3R,5S)-5-aryl-2-benzoylamino-6,7-bis(methoxycarbonyl)-2,3-dihydro-1-oxo-3-phenyl-1H,5H-pyrazolo[1,2-a]-pyrazoles. Synthesis of rel-(2R,3R)-3-phenyl-3-[5-aryl-3,4-bis(methoxycarbonyl)pyrazolyl-1]alanine esters

rel-(2R,3R)-N-Benzoylamino-6,7-bis(methoxycarbonyl)-2,3-dihydro-1-oxo-1H,5H-pyrazolot[1,2-a]-pyrazoles 5 , accesible by cycloaddition of dimethyl acetylenedicarboxylate ( 3 ) to (1Z)-rel-(4R,5R)-1-aryl-methylidene-4-benzoylamino-5-phenyl-3-pyrazolidinone-1-azomethine imines 4 , undergo oxidative ring cleavage with methanolic bromine giving rel-(2R,3R)-N-benzoyl-3-phenyl-3-[5-aryl-3,4-bis(methoxy-carbonyl)pyrazolyl-1]alanine methyl esters 6 as products.     

Sensitized photoxygenation of piroxicam in neat solvents and solvent mixtures.

Detection of O(2)(1Delta(g)) phosphorescence emission, lambda(max)=1270 nm, following laser excitation and steady state methods were employed to determine the total rate constant, k(T), for the reaction between the non-steroidal anti-inflammatory drug piroxicam (PRX) and singlet oxygen in several solvents. Values of k(T) ranged from 0.048+/-0.003 x 10(6) M(-1) s(-1) in chloroform to 71.2+/-2.2 x 10(6) M(-1) s(-1) in N,N-dimethylformamide. The chemical reaction rate constant, k(R), was determined by using thermal decomposition of 1,4-dimethylnaphthalene endoperoxide as the singlet oxygen source. In acetonitrile, the k(R) value is equal to 5.0+/-0.4 x 10(6) M(-1) s(-1), very close to the k(T) value. This result indicates that, in this solvent, the chemical reaction corresponds to the main reaction path. Dependence of total rate constant on the solvent parameters pi* and beta can be explained in terms of a reaction mechanism that involves the formation of a perepoxide intermediate. Rearrangement of the perepoxide to dioxetane followed by ring cleavage and transacylation accounts for the formation of N-methylsaccharine and N-(2-pyridyl)oxamic acid, the main reaction products. Data obtained in dioxane-water (pH 4) mixtures with neutral enolic and zwitterionic tautomers of piroxicam in equilibrium show that the zwitterionic tautomer reacts with singlet oxygen faster than the enolic tautomer.     

Chemistry of 2-Methylene-2,3-dihydrofuran-3-ones: XVIII. Reaction of Oxalyl Chloride with Acetophenone and Dibenzoylmethane

Treatment of acetophenone and dibenzoylmethane with excess oxalyl chloride gave heterocyclization products, 2-(3-oxo-5-phenyl-2,3-dihydrofuran-2-ylidene)-5-phenyl-2,3-dihydrofuran-3-one and a mixture of 4-benzoyl-5-phenyl-2,3-dihydrofuran-2,3-dione with 4-benzoyl-2-dibenzoylmethylene-5-phenyl-2,3-dihydrofuran-3-one.     

Reaction of singlet oxygen with trans-4-propenylanisole. Formation Of

We report the effects of added acid in the reaction of singlet oxygen with trans-4-propenylanisole (1). We provide evidence that solvent acidity modifies the behavior of the transient intermediates. Relative to reactions in aprotic solvent, enhanced dioxetane concentrations are observed in MeOH and in nonprotic solvents with acid. We suggest a new mechanism that invokes a proton transfer from MeOH and benzoic acid to perepoxide (2) and zwitterion (3) intermediates.     

Exclusive formation of alpha-methyleneoxetanes in ketene-alkene cycloadditions. Evidence for intervention of both an alpha-methyleneoxetane and the subsequent 1,4-zwitterion

This paper describes a new mechanistic feature for the Staudinger ketene-alkene cycloaddition reactions to give cyclobutanones. Low-temperature NMR (13C, 19F, and 1H) monitoring of a reaction between bis(trifluoromethyl)ketene (1) and ethyl vinyl ether (2) has shown that the Staudinger reaction proceeds to form initially and exclusively an alpha-methyleneoxetane (3) by [2 + 2](C=O) cycloaddition across the ketene C=O bond. The initial intermediate 3 undergoes ring cleavage to produce a 1,4-zwitterion (4), which is converted to the final [2 + 2](C=C)-type product, cyclobutanone (5). The key intermediate 3 has been isolated in its pure form and was found to be converted to the final products 5 on warming, via the 1,4-zwitterion 4. The alpha-methyleneoxetane 3 is so reactive that it reacts with methanol rapidly even at -80 degrees C via solvolysis to afford an adduct 7. The ion 4 derived from the pure isolated oxetane 3 was intercepted with acetone by a 1,4-dipolar cycloaddition to give a 1,3-dioxane 8. An open-chain alpha,beta-enone (6) has been also obtained from 3. We conclude that the (1 + 2) reaction proceeds in a new three-step mechanism; formation of an alpha-methyleneoxetane 3, a [2 + 2]-type cycloadduct across the C=O bond of ketene, followed by ring cleavage to give the zwitterion 4 and by recombination to form the final product, cyclobutanone 5. The zwitterion 4 is not equilibrating with reactants 1 and 2 but comes from the alpha-methyleneoxetane 3. Exclusive formation of another oxetane 12 has been observed in a reaction between diphenylketene (9) and methyl isopropenyl ether (11). The selectivity of initial formation of cyclobutanone or oxetane has been generalized with aid of frontier-orbital theory and ab initio calculations.     

Palladium(II)-catalyzed oxidation of aldehydes and ketones. 1. Carbonylation of ketones with carbon monoxide catalyzed by palladium(II) chloride in methanol.

Unsubstituted or alkyl-substituted cyclic ketones react with PdCl2 in methanol under a CO atmosphere to give mainly acyclic diesters along with some acyclic chloro-substituted monoesters. The monosubstituted cyclic ketones, 2-hydroxy- and 2-methoxycyclohexanone, do not give ring cleavage but rather produce 2-(carbomethoxy)cyclohex-2-en-1-one. 13CO labeling experiments indicate one CO is inserted in forming the diester product so the second ester group must arise from the original ketone group. Two mechanisms are possible for the diester reaction. One involves initial Pd(II)-CO2CH3 insertion across the double bond of the enol form of the ketone while the second involves initial addition of Pd(II)-OCH3 followed by CO insertion into the new Pd(II)-carbon bond formed. Pd(II) elimination and acid-catalyzed ring cleavage produce the second methyl ester group in both routes. The chloro-substituted monoester is formed by initial Pd(II)-Cl insertion across the double bond followed by the acid-catalyzed ring cleavage. The 2-(carbomethoxy)cyclohex-2-en-1-one must result from elimination of water or methanol from the alpha-ketoester product formed by the initial methoxycarbonylation of the enol form of the ketone. As expected, the acyclic ketone, 2-decanone, formed methyl acetate and a mixture of methyl nonanoate and 1-chlorooctane as products.     

Interactions of singlet oxygen with 2,5-dimethyl-2,4-hexadiene in polar ano non-polar solvents evidence for a vinylog ene-reaction

2,5-Dimethyl-2,4-hexadiene ($\text{1}$)was studied as a singlet oxygen acceptor in various solvents. $\text{1}$undergoes concomitantly the three well-known modes of singlet oxygen reactions: (1) the ene-reaction to give the allylic hydroperoxide $\text{3}$, (2) the (4+2)-cycloaddition to give the endoperoxide $\text{4}$, and (3) the (2+2)-cycloaddition to give the dioxetane $\text{2}$. Beyond that (and in contrast to simple olefins), there are (4) “physical” quenching and (5) a “vinylog ene-reaction” to give the twofold-unsaturated hydroperoxide $\text{5}$. The latter reaction represents a novel mode of singlet oxygen interaction with a substituted 1,3-diene. - Kinetic analysis shows that “physical” quenching, endoperoxide and vinylog ene-product formations proceed with solvent-inde pendent rates; the rates of dioxetane and ene-product formations, however, are solvent-dependent. - A mechanism (Scheme 3) is proposed, according to which endoperoxide formation is due to a concerted singlet oxygen reaction with the s-cis-conformational isomer $\text{1b}$; with the s-trans-isomer $\text{1a}$, “physical” quenching and the vinylog ene-reaction proceed via a non-polar singlet diradical intermediate, whereas the ene-product formation occurs via a per epoxide-like transition state. In aprotic solvents, the dioxetane is mainly formed via a “tight-geometry intermediate”, in methanolic solution via a solvent-stabilized zwitterion; the latter is also responsible for the formation of the methanol-addition product $\text{6}$.     

带有四个不同芳基的环丁烷的合成、结构及光化学性质

通过不同杂芳基乙烯分子间的交叉光二聚反应在硫酸溶液中和中压汞灯照射下,合成了4种含7个不同取代芳基的环丁烷衍生物.用紫外和红外光谱及¹H和¹³CNMR谱确定其结构为顺式头尾相对型二聚体.     

Alkaloids of Siberia and Altai flora: XVIII. Alkyl 2-acetylamino-5-[2-(pyridin-3-yl)vinyl]benzoates in the synthesis of indolizines containing an anthranilic acid ester moiety

Methyl 2-acetylamino-5-[2-(6-methylpyridin-3-yl)vinyl]benzoate reacted with phenacyl bromide to produce quaternary 1-(2-aryl-2-oxoethyl)-2-methyl-5-(4-acetylamino-3-methoxycarbonyl)pyridinium bromides. 1,3-Dipolar cycloaddition of the latter to methyl propynoate and dimethyl but-2-ynedioate gave the corresponding indolizine derivatives containing an anthranilic acid ester moiety. Reactions of acetylenes with N-phenacylpyridinium salts obtained from a diterpene alkaloid derivative, 2-(pyridin-3-yl)vinyl-substituted lappaconitine afforded analogous compounds in which the indolizine fragment is conjugated to the aromatic ring of the alkaloid. 1,3-Dipolar cycloaddition of 1-(2-aryl-2-oxoethyl)-2-methyl-5-(4-acetylamino-3-methoxycarbonyl) pyridinium bromides with methyl propynoate was regioselective.     

Quinazolines and 1,4-benzodiazepines. XLVI. Photochemistry of nitrones and oxaziridines

The cyclic nitrones 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5a ) and 1,3-dihydro-7-methylthio-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5b ) are photoisomerized to readily isolable oxaziridines, 7-chloro-4,5-epoxy-5-phenyl-1,3,4–5-tetrahydro-2H-1,4-benzodiazepin-2-one ( 6a ) and 4,5-epoxy-5-phenyl-1,3,4,5-tetrahydro-7-methylthio-2H-1,4-benzo-diazepin-2-one ( 6b ). Oxaziridine 6b upon further irradiation gave ring expansion and ring contraction products, 4,6-dihydro-2-phenyl-9-methylthio-5H-1,3,6-benzoxadiazocin-5-one ( 7b ) and 4-benzoyl-3,4-dihydro-6-methylthioquinoxalin-2(1H)-one ( 8b ) respectively. The ring contraction product, 4-benzoyl-6-chloro-3,4-dihydroquinoxalin-2(1H)-one ( 8a ), was obtained from irradiation of oxaziridine 6a .