Synthesis of 4‐(2‐hydroxyphenyl)‐1‐phenyl‐1,2,4‐triazolidine‐3,5‐dione derivatives through cyclic transformations of 3‐(2‐phenylcarbazoyl)‐2(3H)‐benzoxazolone derivatives

Four 3‐(3‐benzylidene‐2‐phenylcarbazoyl)‐2(3H)‐benzoxazolone derivatives 3 have been synthesized from benzoxazolone derivatives 1 and benzaldehyde N‐chloroformylphenylhydrazone 2. By acid hydrolysis, these compounds yielded 3‐(2‐phenylcarbazoyl)‐2(3H)benzoxazolone derivatives 4 which were not isolated and were transformed via an intramolecular reaction into 4‐(2‐hydroxyphenyl)‐1‐phenyl‐1,2,4‐triazolidine‐3,5‐dione derivatives 5 in a good yield. Attempts to cyclize these compounds by intramolecular elimination of water into tricyclic compounds 6 with various dehydrating agents were unsuccessful.     

Synthesis of 4,12-dihydro-4-oxoquino-[1,8a,8-a,b]quinoxaline-5-carboxylic acid derivatives

The synthesis and antibacterial activity of 1-substituted amino-2-fluoro-4,12-dihydro-4-oxoquino[1,8a,8-a,b]quinoxaline-5-carboxylic acid derivatives are described. The synthetic route includes a carbon homologation and two intramolecular nucleophilic displacement cyclization reactions leading to the novel 4,12-dihydro-4-oxoquino[1,8a,8-a,b]quinoxaline-5-carboxylic acid heterocycle.     

Rhenium-catalyzed regioselective synthesis of multisubstituted pyridines from β-enamino ketones and alkynes via C-C bond cleavage

A new method is described for the regioselective synthesis of multisubstituted pyridine derivatives. Treatment of N-acetyl β-enamino ketones with alkynes in the presence of the rhenium catalyst, Re(2)(CO)(10), gives multisubstituted pyridines regioselectively. In this reaction, the N-acetyl moieties are important for the selective formation of the multisubstituted pyridines. This reaction proceeds via insertion of alkynes into a carbon-carbon single bond of β-enamino ketones, intramolecular nucleophilic cyclization, and elimination of acetic acid.     

δ-Nitroalkanols as precursors for the one-pot synthesis of substituted tetrahydrofurans

DBU catalyses the one-pot Michael addition of nitroalkanes to 1,4-dienone derivatives, elimination of nitrous acid, then intramolecular conjugate addition-ring closure to allow the direct formation of a variety of tetrahydrofurans.     

Hydrogen migrations in mass spectrometry. VI—the chemical ionization mass spectra of substituted benzoic acids and benzyl alcohols

The H₂ and CH₄ chemical ionization mass spectra of a series of series of substituted benzoic acids and substituted benzyl alcohols have been determined. For the benzoic acids the major fragmentation reactions of the protonated molecule involve elimination of H₂O or elimination of CO₂, the latter reaction involving migration of the carboxylic hydrogen to the aromatic ring. For the benzyl alcohols the major fragmentation reactions of [MH]⁺ involve loss of H₂O or CH₂O, analogous to the CO₂ elimination reaction for the benzoic acids. It is shown that the CO₂ and CH₂O elimination reactions occur only when a conjugated aromatic ring system is present, and that for the carboxylic acid systems, methyl groups and, to a lesser extent, phenyl groups are capable of migrating. The only discernible effect of substituents on the fragmentation of [MH]⁺ is an enhancement of the H₂O loss reaction in the benzoic acid system when an amino, hydroxyl, or halogen substituent is ortho to the carboxyl function. This ‘ortho’ effect, which differs in scope from that observed in electron impact mass spectra, is attributed to an intramolecular catalysis by the ortho substituent of the 1,3 hydrogen migration in the carbonyl protonated acid followed by H₂O elimination. Apparently, this route is favoured over the direct elimination of H₂O from the carbonyl protonated acid, since the latter has a high activation energy barrier because of unfavourable orbital symmetry restrictions.     

How Does Acetylcholine Lose Trimethylamine? A Density Functional Theory Study of Four Competing Mechanisms

Low-energy collision-induced dissociation (CID) of acetylcholine (ACh) yields only two fragment ions: the dominant C(4)H(7)O(2)(+) ion at m/z 87, arising from trimethylamine loss; and protonated trimethylamine at m/z 60. Since the literature is replete with conflicting mechanisms for the loss of trimethylamine from ACh, in this article density functional theory (DFT) calculations are used to assess four competing mechanisms: (1) Path A involves a neighboring group attack to form a five-membered ring product, 2-methyl-1,3-dioxolan-2-ylium cation; (2) Path B is a neighboring group attack to form a three-membered ring product, 1-methyl-oxiranium ion; (3) Path C involves an intramolecular elimination reaction to form CO protonated vinylacetate; and (4) Path D is a 1,2-hydride migration reaction forming CH(2)-protonated vinylacetate. At the MP2/6-311++G(2d,p)//B3-LYP/6-31+G(d,p) level of theory path A is the kinetically favored pathway, with a transition-state energy barrier of 37.7 kcal mol(-1) relative to the most stable conformer of ACh. The lowest energy pathway for the formation of protonated trimethylamine was also calculated to proceed via path A, involving proton transfer within the ion-molecule complex intermediate, with the exocylic methyl group being the proton donor. To confirm the site of proton transfer, low-energy CID of acetyl-d(3)-choline (d(3)-ACh) was carried out, which revealed loss of trimethylamine and the formation of Me(3)ND(+).     

Synthesis of polybenzamide–ureas from N-mesyloxyphthalimide and diamines

Novel polybenzamide-ureas have been synthesized by the polymerization of N-mesyloxyphthalimide with diamines in N-methyl-2-pyrrolidone in the presence of acid acceptors. The polymerization probably proceeds through the formation of ring-opened adducts, followed by elimination and rearrangement yielding 2-isocyanatobenzamide derivatives, which were subsequently reacted to give polybenzamide-ureas. These polymers had inherent viscosities of 0.12–0.34 and were soluble in a wide range of solvents, including pyridine and m-cresol, as well as polar aprotic solvents. All of the polymers had low softing temperatures in the range of 140–260°C, and thermal analyses showed that marked decomposition of the polymers occurred at around 200–300°C, presumably forming quinazolinedione rings by intramolecular deamination.     

Four-Component Synthesis of Disubstituted 1,3,4-Oxadiazoles from N-Isocyaniminotriphenylphosphorane,Phenylacetylenecarboxylic Acid,Chloroacetone Derivatives,and Primary Amines

The 1:1 imine intermediate generated by the addition of primary amine to chloroacetone derivatives is trapped by N-isocyaniminotriphenylphosphorane in the presence of phenylacetylenecarboxylic acid, leading to the formation of the corresponding iminophosphorane intermediate. Disubstituted 1,3,4-oxadiazole derivatives are formed via intramolecular aza-Wittig reaction of the iminophosphorane intermediate. The reactions were completed in neutral conditions at room temperature. The disubstituted 1,3,4-oxadiazole derivatives were prepared in excellent yields.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Synthesis of benzo- and naphtho-fused bicyclo[n.3.1]alkane frameworks with a bridgehead nitrogen function by palladium-catalyzed intramolecular α'-arylation of α-nitroketones

The C-alkylation of cyclic α-nitroketones with α-halobenzyl halides in the presence of DBU followed by a Pd-catalyzed intramolecular C-arylation afforded benzo-and naphtho-fused bicyclo[n.3.1]alkane derivatives (n = 3, 4, 5) in excellent overall yields for the two-step sequence. In some of the reactions starting from α-nitrocyclooctanone, the major products were fused indane derivatives arising from an intramolecular attack of an intermediate Pd species onto the carbonyl group, followed by elimination.     

Application of aminopropyltriethoxysilane and <Emphasis Type="Italic">N</Emphasis>-[2-(aminoethyl)-<Emphasis Type="Italic">N</Emphasis>-3-(trimethoxysilyl)propyl]amine to the synthesis of linear and heterocyclic compounds

Reaction of 3-aminopropyltriethoxysilane and N-[2-(aminoethyl)-N-3-(trimethoxysilyl)propyl]-amine and their derivatives with diethylcarbamic acid trimethylsilyl ether and trimetisilylisocyanate proceeds through the stage of formation of intermediate products which under conditions of the synthesis undergo intramolecular (in the case of formation O-silylcarbamates) and intermolecular (in the case of the formation of carbamide trimethylsilyl derivatives) desilylation leading to the cyclic and linear products respectively.     

Lewis Acid-Mediated Ring Contraction of 2,4-Diaryl-2,3-dihydro-1H-1,5-benzodiazepines: Access to 2-Aryl-1-styrylbenzimidazoles

2,4-Diaryl-2,3-dihydro-1H-1,5-benzodiazepines readily undergo a ring contraction to generate 2-aryl-1-styrylbenzimidazoles in the presence of some Lewis acids. Copper acetate shows high efficiency compared with other Lewis acids. The ring contraction includes Lewis acid-catalyzed intramolecular addition, ammonium-induced ring-opening of the generated four-membered azetidine ring, deprotonation, and amine-promoted nucleophilic styryl 1,2-shift and elimination. Copper acetate serves as Lewis acid, base, and oxidant. The current reaction provides an efficient method for the convenient synthesis of 2-aryl-1-styrylbenzimidazole derivatives from readily available 2,4-diaryl-2,3-dihydro-1H-1,5-benzodiazepines.     

Synthesis of 6‐Alkylidene‐5,6‐dihydro‐4H‐1,3‐thiazine Derivatives via the Cyclization of N‐3‐Bromo‐3‐alkenylthioamides

By the treatment of N‐3‐bromo‐3‐alkenylthioamides with sodium hydroxide in DMF‐H₂O in the presence of tetra‐butylammonium bromide, series of 6‐alkylidene‐5,6‐dihydro‐4H‐1,3‐thiazine derivatives were prepared in moderate to good yields. The cyclization is supposed to proceed via both the intramolecular vinylic nucleophilic substitution and the elimination‐addition mechanisms (formation of acetylenic intermediates) in a competitive manner.     

A comparative study of the pyrolytic and electron impact-induced fragmentations of 4-phenylbutanoic acid and some analogues

By use of deuterium labelling it is shown that the mechanisms of fragmentation of the title compounds upon Curie-point pyrolysis and electron impact are essentially different. For example, the pyrolytic expulsion of water from 4-phenylbutanoic acid is a 1,2 eliminations, whereas upon electron impact water is expelled via a 1,4 elimination; the generation of styrene from this acid proceeds via a concerted mechanism upon pyrolysis, but via a stepwise mechanism upon electron impact.     

Substituted 3-phenylpropenoates and related analogs: electron ionization mass spectral fragmentation and density functional theory calculations

Analysis of ethyl 3-(2-chlorophenyl)propenoate by electron ionization mass spectrometry showed the distinct loss of an ortho chlorine. To characterize the structural requisites for the observed mass fragmentation, a series of 30 halogen-substituted 3-phenylpropenoate-related structures were examined. All ester-containing alkene derivatives exhibited loss of the distinctive chlorine from the 2-position of the phenyl ring. Analogous derivatives with the halogen (chlorine or bromine) in the para position did not evidence selective halogen loss. Results demonstrated that substituted 3-phenylpropenoates and their analogs fragment via the formation of a previously reported benzopyrylium intermediate. To understand the correlation between the intramolecular radical substitution and the abundance and selectivity of the chlorine (or other halogen) displacement, density functional theory calculations were performed to determine the charge on the principal cation involved in the chlorine loss (in the ortho, meta, and para positions), the charge for the neutral radical (noncation), the excess alpha-electron density on the relevant atom and the energy to form the cation from the neutral atom (ionization energy). Results showed that the selectivity and extent of halogen displacement correlated highly to the electrophilicity of the radical cation as well as the neutral radical. These data further support the proposed fragmentation mechanism involving intramolecular radical elimination.     

Le mécanisme de la réduction polarographique des dérivés ditosyloxylés et son implication en électrochimie préparative

The cleavage of a single SO₂? O bond occurs during the polarographic reduction of a tosyloxy group (p? CH₃C₆H₄SO₂O = TsO) in aprotic medium and intramolecular cyclisation may ensue when a second TsO group is present on the same molecule. The polarographic behaviour of aliphatic ditosyloxy derivatives is discussed on the assumption that oriented vicinal derivatives at the interface assume a conformation which resembles the geometry of the transition state for an intramolecular elimination with anchimeric assistance of one of the tosyloxy groups. This situation favours the electron transfer, whereas the same geometric requirements hinder the intramolecular interaction of the TsO groups of the oriented non-vicinal derivatives. This interpretation agrees well with the fact that the large scale electrolysis of vicinal ditosyloxy derivatives give much higher yield of cyclic ethers than the higher homologues. It is also shown that intramolecular interaction between TsO groups can occur through an intervening double bond in a non-vicinal derivative.     

The role of benzoic acid in proline‐catalyzed asymmetric michael addition: A density functional theory study

In asymmetric Michael addition between ketones and nitroolefins catalyzed by L ‐proline, we observed that it was benzoic acid or its derivatives rather than other proton acid that could accelerate the reaction greatly, and different benzoic acid derivatives brought different yields. To explain the experimental phenomena, a density functional theory study was performed to elucidate the mechanism of proline‐catalyzed asymmetric Michael addition with benzoic acid. The results of the theoretical calculation at the level of B3LYP/6‐311+G(2df,p)//B3LYP/6‐31G(d) demonstrated that benzoic acid played two major roles in the formation of nitroalkane: assisting proton transfer and activating the nitro group. In the stage of enamine formation from imine, the energy profiles of benzoic acid derivatives were also calculated to investigate the reasons why different benzoic acid derivatives caused different yields. The results demonstrated that the pK_a value was the major factor for p‐substituted benzoic acid derivatives to improve the yields, whereas for m/o‐substituted benzoic acid derivatives, both pK_a value and electronic and steric effects could significantly increase the yields. The calculated results would be very helpful for understanding the reaction mechanism of Michael addition and provide some insights into the selection of efficient additives for similar experiments. © 2012 Wiley Periodicals, Inc.     

One‐Pot,Four‐Component Synthesis of Fully Substituted 1,3,4‐Oxadiazole Derivatives from (Isocyanoimino)triphenylphosphorane,a Primary Amine,an Aromatic Carboxylic Acid,and Chloroacetone

The 1 : 1 imine intermediate 7 generated by the addition of a primary amine 2 to chloroacetone ( 1 ) is trapped by (isocyanoimino)triphenylphosphorane ( 4 ) in the presence of an aromatic carboxylic acid 3 and leads to the formation of the corresponding iminophosphorane intermediate 9 (Scheme 2). The 1,3,4‐oxadiazole derivatives 5 are then formed via an intramolecular aza‐Wittig reaction of the iminophosphorane intermediate 9 . The reactions were completed under neutral conditions at room temperature. The fully substituted 1,3,4‐oxadiazole derivatives 5 were produced in high yields (Table).     

Carbohydrates as Chiral Auxiliaries in Stereoselective Synthesis. New Synthetic Methods (90)

Carbohydrates are inexpensive natural products in which numerous functional groups and stereogenic centers are combined in one molecule. By directed regio-and stereoselective formation of derivatives they can be converted into efficient chiral auxiliaries for controlling asymmetric syntheses. Stereoelectronic effects and pre-orientation of the reactive and shielding groups through formation of complexes can often be used for effective diastereofacial differentiation. In aldol reactions and alkylations on carbohydrate ester enolates intramolecular complexation promotes simultaneous elimination with formation of ketene. The steric, stereoelectronic, and coordinating properties of carbohydrate templates can also be used selectively to attain high levels of asymmetric induction in processes such as Diels–Alder reactions, hetero-Diels–Alder reactions, [2 + 2] cycloadditions, cyclopropanations, and Michael additions. It was possible with bicyclic, strongly stereodifferentiating carbohydrate auxiliaries to achieve a diastereoselective synthesis of carboxylic acid derivatives branched in the β position by a new 1,4-addition of alkylaluminum halides to α,β-unsaturated N-acylurethanes, in which methylaluminum halides and higher alkyl- or arylaluminum compounds behave mechanistically in a strikingly different manners. As complex ligands in chiral reagents and promoters, carbohydrates allow highly stereoselective reductions and aldol reactions that lead, amongst others, to chiral alcohols and β-hydroxy-α-amino acids in excellent enantiomeric excesses. Glycosylamines offer the possibility of versatile stereoselective applications: in the presence of Lewis acids the corresponding aldimines permit high-yielding syntheses of enantiomerically pure α-amino acids by Strecker and Ugi reactions, controlled by steric and stereoelectronic effects and by complex formation. They can be used with equal efficiency for asymmetric syntheses of chiral homoallylamines and for asymmetric Mannich syntheses of β-amino acids and chiral heterocycles, for example alkaloids.     

Synthesis of Novel 2‐Oxoquinoline Derivatives via Ugi‐Four‐Component‐Heck Reaction

The present study provides an efficient strategy for the preparation of novel N‐substituted‐4‐methyl‐quinolin‐1(2H)‐one derivatives via two‐step Ugi/Heck reaction. The procedure is based on the Ugi coupling between 2‐bromoanilines, various aromatic aldehydes, vinylacetic acid, and isocyanides, and then intramolecular Heck reaction, which leads to the formation of the title compounds in good yields.     

Cobalt-Catalyzed Intramolecular Hydroacylation Involving Cyclopropane Cleavage

A simple cobalt-diphosphine catalyst has been found to efficiently promote intramolecular cyclization of ortho-cyclopropylvinyl- and cyclopropylidenemethyl-substituted benzaldehydes into benzocyclooctadienone and benzocycloheptadienone derivatives, respectively. This ring-opening hydroacylation likely involves aldehyde C−H oxidative addition, olefin insertion, cyclopropane cleavage by β-carbon elimination, and C−C bond-forming reductive elimination, as was supported by mechanistic experiments and DFT calculations.