Substituent-controlled domino-Knoevenagel-hetero Diels-Alder reaction—a one-pot synthesis of polycyclic heterocycles

The reaction of 2-(N-alkenyl-N-aryl)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde with dimedone/Meldrum’s acid/4-hydroxycoumarin by heating in ethanol in the presence of pyridine produces polycyclic heterocycles bearing pyridine and pyran rings in a one-pot reaction. The effect of substituents on N-atom of the amino function controls the mode of reaction. Terminal alkenes prefer intramolecular Michael type reaction, but non-terminal alkenes favour Diels-Alder reaction, whereas, under similar condition, 2-(N-alkyl-N-allyl)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde undergoes domino-Knoevenagel-hetero Diels-Alder reaction.     

Reactions of N,N-dimethylamino(diphenylphosphoryl)chloromethane with alkan-2-ones

The direction of the reaction of N,N-dimethylamino(diphenylphosphoryl)chloromethane with alkan-2-ones depends on the ketone structure. N,N-Dimethylamino(diphenylphosphoryl)-chloromethane reacts with linear alkan-2-ones following the Abramov-type reaction to give α-phosphorylated alcohols, while the reaction with branched alkan-2-ones and acetophenone proceeds as the Mannich-type reaction affording the phosphorylated Mannich bases.     

Synthesis of fluorinated imines and carbodiimides from azides via aza-Wittig reaction

The Staudinger reaction of fluoroalkylazides were studied. A series of N-fluoroalkylimines were synthesized via aza-Wittig reaction of N-fluoroalkyliminophosphoranes. The N,N′-difluoroalkylated carbodiimide was also synthesized via the reaction of N-fluoroalkyliminophosphoranes with carbon dioxide or carbon disulfide.     

Verbanone in the synthesis of amidoketones from o-menthane series

A verbanone reaction with acetonitrile under Ritter reaction conditions led to a selective formation of o-menthane derivatives, a mixture of stereoisomeric cis-and trans-8-acetamido-o-menthones. The streoisomers ratio depends on the reaction conditions and the character of acid catalyst used.     

Chiral base-catalyzed aldol reaction of trimethoxysilyl enol ethers: effect of water as an additive on stereoselectivities

An aldol reaction of trimethoxysilyl enol ether catalyzed by lithium binaphtholate is described. The aldol reaction of trimethoxysilyl enol ether derived from cyclohexanone under anhydrous conditions predominantly afforded the anti-aldol adduct with moderate enantioselectivity, whereas the reaction under aqueous conditions predominantly resulted in the syn-adduct and the enantioselectivity of the syn-adduct was considerably improved. The best enantioselectivity was obtained in the reaction of trimethoxysilyl enol ether derived from 1-indanone with cyclohexanecarboxaldehyde (97% ee (syn)). This is the first example of an aldol reaction of trimethoxysilyl enol ether catalyzed by a chiral base.     

Kinetic parameters of radical reactions of 2-mercaptobenzothiazole with quinone imines

The chain reaction of N,N′-diphenyl-1,4-benzoquinone diimine with 2-mercaptobenzothiazole was studied by two methods developed earlier for the nonchain reaction of N-phenyl-1,4-benzoquinone monoimine with 2-mercaptobenzothiazole. In the methods used, the kinetic scheme of the reaction is simplified by creating conditions under which the rates of all stages except radical generation and decay can be neglected. One of the methods was updated. For the nonchain reaction of N-phenyl-1,4-benzoquinone monoimine with 2-mercaptobenzothiazole, both methods gave close results; for the chain reaction of N,N′-diphenyl-1,4-phenylenediamine with 2-mercaptobenzothiazole, the results differed by approximately one order of magnitude.     

Investigation of m-nitroaniline formation during the Zimmermann reaction

The Zimmermann reaction for the determination of 17-ketosteroids was tested under both room-temperature and steam-distillation reaction conditions. meta-Nitroaniline was isolated from the residue of the steam distillation by ether extraction and thin-layer chromatography. Conclusive identification was by infrared spectroscopy. In contrast, m-nitroaniline was not formed under room-temperature reaction conditions, even when allowed to react for 24 hr. Similar results were also obtained for the reaction between acetone and m-dinitrobenzene under alkaline conditions. In conclusion, the results indicate that m-nitroaniline formation cannot account for the conversion of structure I to structure II under room-temperature reaction conditions as investigated herein.     

N-Tosylaziridine, a new substrate for chemical fixation of carbon dioxide via ring expansion reaction under atmospheric pressure

N-Tosylaziridine was found to be a useful substrate for cycloaddition reaction with carbon dioxide. The reaction was successfully catalyzed by lithium bromide under atmospheric pressure to give the corresponding five-membered cyclic urethane, N-tosyl-1,3-oxazolidin-2-one, selectively. It was found that electron-donating nature of the substituent at 2-position of N-tosylaziridine accelerated the reaction, and this tendency allowed us to estimate the reaction mechanism.     

Solid state reaction between p-benzoquinone and dihydroxybenzene

Reaction kinetics of p-benzoquinone-p-dihydroxybenzene; p-benzoquinone-m-dihydroxybenzene and p-benzoquinone-o-dihydroxybenzene systems have been studied in the solid state using capillary, gravimetric, and dilatometric techniques. It is found that p-benzoquinone is the diffusing species. The diffusion occurs through surface migration and depends very much on the symmetry of the dihydroxybenzene molecules. Gravimetric studies indicate that cracks are formed in the product during reaction and that the reaction reaches completion. Dilatometric studies indicate that the reaction products are more compact and contraction in volume takes place during the course of reaction.     

Rheological study on the cure kinetics of two-component addition cured silicone rubber

The cure kinetics for two-component silicone rubber formed by addition reaction was studied by the rheological method. The influence of reaction temperature (T) on the cure kinetics was explored in detail. It was observed that the data of gel time (t _gel, i.e. the time when the reaction reaches the gel point) or a specific reaction time (t _nc) (defined as the reaction time before which time the influence of confinement of network on the diffusion of reaction components can be neglected) versus T obey certain functional relationship, which was well explained by the cure kinetics model of thermoset network. The cure kinetics for the two-component silicone rubber can be well fitted by the Kamal-Sourour(autocatalyst) reaction model rather than Kissinger model. When the reaction time was before or equal to t _nc, the reaction order obtained by the Kamal-Sourour reaction model was 2, which was consistent with the reaction order inferred from the two components chemical reaction when the diffusion of reaction components was not influenced by the formed cross-linked polymer network. When the reaction time was larger than t _nc, such as to the end of reaction (t _e), the influence of confinement of network on the diffusion of reaction components cannot be neglected, and the reaction order obtained by the Kamal-Sourour reaction model was larger than 2. It was concluded that the confinement effect of network had a greater influence on the cure kinetics of the silicone rubber. The reaction rate constants (k _r) under different temperatures were also determined by Kamal-Sourour reaction model. The activation energy (E) for the two-component silicone rubber was also calculated from the results of lnt _gel, lnt _nc, and lnk _r versus 1/T, respectively. The three values of E were close, which indicated that above analyses were self-consistent.     

Application of ortho-chloro-β-aroylthioamides in synthesis(II): an efficient one-pot, three-component synthesis of tricyclic thiochromeno[2,3-b]pyridine derivatives

Tricyclic thiochromeno[2,3-b]pyridine derivatives have been successfully synthesized in an unusual one-pot multicomponent cascade reaction from ortho-halo-β-aroylthioamides, Meldrum's acid, and aromatic aldehydes. The reaction presumably proceeds via Knoevenagel condensation-Michael addition-cyclocondensation-decarboxylation-rearrangement-intramolecular S_NAr reaction sequence. High bond forming efficiency of this reaction makes it attractive for the synthesis of thiochromeno[2,3-b]pyridine derivatives in a single step operation.     

Stereoselective total synthesis of (+)-(6R,2′S)-cryptocaryalactone and (−)-(6S,2′S)-epi cryptocaryalactone via asymmetric acetate aldol reaction

The total synthesis of (+)-(6R,2′S)-cryptocaryalactone and (?)-(6S,2′S)-epi cryptocaryalactone is reported based on asymmetric acetate aldol reaction. Still–Gennari reaction, Evans acetal intramolecular oxa-Michael reaction and lactonisation are the key steps in the target synthesis.     

Iodine-catalyzed coupling of β-hydroxyketones with aromatic amines to form β-aminoketones and Benzo[h]quinolones

An iodine-catalyzed coupling of β-hydroxyketones with aromatic amines to yield β-aminoketones and benzo[h]quinolones had been developed. Noble metallic catalysts, oxidants, α, β-unsaturated ketone intermediates and aza-Michael addition were not involved in this coupling reaction which made it unique when compared to other reactions reported in literature. Inexpensive iodine catalyst, easy accessible raw materials, mild reaction conditions, good functional group tolerance and excellent selectivity made this coupling reaction be a practical method. This reaction can also be scaled up.     

N-Allyl-1,3-oxazines via a facile keto-ene/cyclization tandem reaction

The intramolecular keto-ene/cyclization tandem reaction of γ-N-allylamino ketones is an effective means of producing 1,3-oxazines. The reaction usually requires high temperatures and/or pressures. We discovered that N,N-diallyl amines undergo the reaction at lower temperatures than their monoallyl analogs. An extreme example, 1-N,N-diallylamino-9,10-anthraquinone, undergoes the keto-ene reaction near ambient temperature. In the case of 1-N,N′-dialkylaminoanthraquinones, electron deficient ene components can even be used, allowing the preparation of a broad spectrum of oxazines. Furthermore, the N-allyl-1,3-oxazine can be easily deallylated to produce a 1,3-oxazine that contains a secondary amine.     

Asymmetric synthesis of α,β-substituted γ-amino acids via conjugate addition

The first conjugate addition reaction of organocuprates to N-enoyl oxazolidinone where a N-protected γ-nitrogen atom and an α-methyl group are present into α, β-unsaturated system is described. This reaction gave anti-products in moderate yields and high diastereomeric ratios. The anti-products have two contiguous stereogenic centers, one formed by the conjugate addition reaction and the other by a diastereoselective protonation reaction. The removal of chiral oxazolidinone moiety and N-deprotection of amino group furnished chiral α, β-disubstituted γ-amino acids.     

Temperature vs. time sequences to palliate deactivation in parallel and in series-parallel with the main reaction: parametric study

The calculation of temperature vs. time sequences to palliate catalyst deactivation in an integral reactor has been studied either by maintaining constant the conversion at the reactor outlet in a simple reaction or by maintaining constant the concentration of a given component at the outlet in a complex reaction system. The experimental systems studied, which are a simple one (dehydration of 2-ethylhexanol) and a complex one (isomerization of cis-butene), have kinetic models of the Langmuir-Hinshelwood-Hougen-Watson type for the main reaction and deactivation, with deactivation by coke dependent on the concentration of the reaction components. In the reaction of dehydration of 2-ethylhexanol deactivation occurs in parallel with the main reaction and in the isomerization of cis-butene deactivation occurs in series-parallel with the main reaction. A parametric study has been carried out for both reaction systems. The sequences calculated have been experimentally proven in an automated reaction apparatus.     

Synthesis of cis bis-β-lactams via Staudinger cycloaddition reaction using C2-symmetric 1,2-diamines

An efficient stereoselective synthesis of bis-β-lactams via cycloaddition reaction (Staudinger reaction) of ketenes with bisimines derived from C₂-symmetric 1, 2-diamines is described. The reaction provided diastereomeric mixture of meso and C₂-symmetric cis-bis-β-lactams with higher selectivity for meso-bis-β-lactams.     

A mild and efficient synthesis of a chiral pyridazinone derivative

We found a mild and efficient reaction condition for construction of a chiral 5-methyl-4,5-dihydropyridazin-3(2H)-one from a chiral β-methyl γ-ketocarboxylic acid via the corresponding acid hydrazide without racemization. Furthermore, we demonstrated that this two-step reaction can be attained by one-pot reaction. This method could be applied to various kinds of substrates because of the mild reaction conditions.     

Isocyanide based multicomponent reactions of oxazolidines and related systems

N-Alkyloxazolidines react in a multicomponent reaction with carboxylic acids and isocyanides to give N-acyloxyethylamino acid amides. The previously reported reaction conditions were improved using a design of experiments approach (DoE). Under the optimised conditions, good yields of the N-acyloxyethylamino acid amide products are obtained both via a three- or four-component approach from N-alkylethanolamines, aldehydes/ketones, isocyanides and carboxylic acids. The reaction of oxazolidines without a nitrogen substituent was found to give either the expected Ugi products or the N-acyloxyethylamino acid amides depending on the choice of reaction conditions. Optimised reaction conditions were also developed for the ring-expansion of oxazolidines to morpholin-2-ones via reaction with an isocyanide followed by hydrolysis. The mechanistic pathway of the multicomponent reaction was briefly investigated using an ¹⁸O labelling experiment. The carboxylic acid component can be replaced by a range of other acidic nucleophiles including thiobenzoic acid, thiophenol or 5-phenyltetrazole, which are incorporated via an alternative pathway. These latter reactions can also be applied to 2-aminotetrahydrofurans, 2-aminotetrahydropyrans or 4-hydroxybut-2-one, further extending the structural diversity of the multicomponent reaction products.     

A room temperature one-pot Knoevenagel-Chan-Evans-Lam coupling reaction for synthesis of N-aryl-2-Iminocoumarins in bio-mass-derived green solvent 2-methylTHF

An efficient approach for the synthesis of biologically interesting N-aryl-2-iminocoumarins by a copper-catalyzed one-pot procedure has been developed by the reaction of 2-hydroxybenzaldehydes, malononitrile and arylboronic acids using triethylamine as a base in a bio-mass-derived green solvent 2-MethylTHF at room temperature. This protocol allows access to several N-aryl-2-iminocoumarins in high yields in a relatively short period of time under mild reaction conditions. The procedure operates by a simple telescoped process wherein 2-imino-2H-chromene-3-carbonitriles are formed in situ by the reaction of 2-hydroxybenzaldehyde, malononitrile, and TEA. Further a subsequent one-pot reaction of imine with the arylboronic afforded the target compounds. To understand the reaction mechanism, MALDI-ESI studies were performed, which showed the in situ generated iminocoumarins to be in ligation cooper to form a copper-iminocoumarin complex thus facilitating the smooth formation of N-aryl-2-iminocoumarins in the reaction. Overall, this protocol is practically valuable, useful in organic synthesis, shows good functional group tolerance and provides access to a diverse array of N-aryl-2-iminocoumarins derivatives.